Skip to main content
Article thumbnail
Location of Repository

Identification of Tumour Associated Antigens as Potential Targets for the Immunotherapy of B-cell Chronic Lymphocytic Leukaemia (B-CLL)

By Hind Abdulrazak Yassin Abdulmajed


B-CLL, the most common adult B-cell malignancy in USA and the western world, is characterized by the accumulation of CD5+ mature B-cells in blood, bone marrow and lymphoid tissues. Many cases require no treatment because of an indolent course, while other patients become symptomatic or develop signs of rapid progression. Treatment is usually non-curative and is directed at reducing the symptoms. However, new therapies are currently under investigation aiming to achieve a curative therapy for B-CLL. The increasing understanding of how peptide antigens are processed, transported and presented by HLA, the identification of tumour antigens recognised by cytotoxic T lymphocytes and the identification of T-cell epitopes on human tumor cells, have opened the routes for the development of more efficient strategies for tumour immunotherapy. Several antigens have been characterized as tumour associated antigens (TAA) in B-CLL, with the potential to elicit specific anti-tumour responses. This thesis addresses the role of survivin, a member of the family of inhibitor of apoptosis proteins, as a potential target for the immunotherapy of B-CLL. Data on survivin expression showed no/ little expression of survivin in resting B-CLL, which was upregulated by in vitro activation with CD40 ligation, CpG-oligodeoxynucleotides (ODN), and with both stimulators together. CD40 ligation resulted in greater B-CLL cell activation, survivin expression, upregulation of activation markers (CD54, CD80 and CD86), and in enhanced activity of B-CLL cells to stimulate allogeneic T cell proliferation, compared to the other two ways of stimulation. Studying the induction of autologous tumour specific T cell responses in vitro, CD40L activated B-CLL cells enhanced CTL responses compared to unactivated cells. No significant difference in response of B-CLL patients T cells to survivin peptide pulsed T2 cells was found between HLA-A2+ and HLA-A2- patients, and no clear peptide specific responses were seen in either group. After investigating survivin peptides for their potential to induce cytotoxic T cell responses, generating survivin specific CTL line from a healthy donor was attempted using peptide pulsed autologous monocyte derived dendritic cells, but was unsuccessful suggesting that no T cells in the culture were able to recognise survivin peptides, or that the culture conditions used were inappropriate for the generation and maintenance of such responses. Finally, in investigation of other TAA expression in B-CLL cells, no expression of MAGE-A1, MAGE-A3, Proteinase-3, WT-1 was detected pre- and post CD40 activation. Positive PRAME expression was detected in 8 out of 20 CD40L activated CLL cells whilst NY-ESO-1 showed an upregulation in one sample. Overall results indicate that much work is still needed to study the potential of immunotherapy in the treatment of B-CLL

Publisher: University of Leicester
Year: 2008
OAI identifier:

Suggested articles


  1. (1989). A collagenbinding 59-kd protein (fibromodulin) is structurally related to the small interstitial proteoglycans PG-S1 and PG-S2 (decorin)."
  2. (2001). A fresh look at tumor immunosurveillance and immunotherapy."
  3. (1991). A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma."
  4. (2005). A listing of human tumor antigens recognized by T cells:
  5. (2001). A listing of human tumor antigens recognized by T cells."
  6. (1995). A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma."
  7. (1999). A new era for cancer immunotherapy based on the genes that encode cancer antigens."
  8. (1995). A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma."
  9. (1994). A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas."
  10. (1997). A new immunobiological view of radiation-promoted lymphomagenesis."
  11. (1981). A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis."
  12. (1997). A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma."
  13. (1999). A novel anti-apoptosis gene: Reexpression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers."
  14. (1998). A survey of the humoral immune response of cancer patients to a panel of human tumor antigens."
  15. (1997). A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening."
  16. (2003). Abnormal T-cell function in B-cell chronic lymphocytic leukaemia."
  17. (2001). Achieving optimal outcomes in chronic lymphocytic leukaemia."
  18. (1995). Activated human NK cells can stimulate resting B cells to secrete immunoglobulin."
  19. (2004). Advances in the use of monoclonal antibodies in the therapy of chronic lymphocytic leukemia."
  20. (1999). Advances in vaccine adjuvants."
  21. (2002). ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1-restricted CD8+ T-cell epitopes."
  22. (2003). ALK-positive diffuse large Bcell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases."
  23. (2000). Allogeneic bone marrow transplantation for low-grade lymphoma and chronic lymphocytic leukemia."
  24. (1992). Amplification of a gene encoding a p53-associated protein in human sarcomas."
  25. (1999). An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in B-chronic lymphocytic leukemia."
  26. (1995). Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity."
  27. (2000). Antibody response to the tumor-associated inhibitor of apoptosis protein survivin in cancer patients."
  28. (2002). Antigen-specific CD4+ T-cell help is required to activate a memory CD8+ T cell to a fully functional tumor killer cell."
  29. (2003). Antigen-specific immunotherapy and cancer vaccines."
  30. (1991). Antigenic stimulation and the occurrence of chronic lymphocytic leukemia."
  31. (2000). Antitumor vaccination: where we stand."
  32. (2004). Apoptotic tumor cells are superior to tumor cell lysate, and tumor cell RNA in induction of autologous T cell response in B-CLL."
  33. (2002). Autologous and allogeneic stem cell transplantation for chronic lymphocytic leukemia."
  34. (2003). B-cell chronic lymphocytic leukaemia: a polymorphic family unified by genomic features."
  35. (2002). B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigenexperienced B lymphocytes."
  36. (2004). B-cell chronic lymphocytic leukemia with aberrant CD8 expression: genetic and immunophenotypic analysis of prognostic factors."
  37. (2005). B-cell lymphomas differ in their responsiveness to CpG oligodeoxynucleotides."
  38. (2002). B-chronic lymphocytic leukemia: practical aspects."
  39. (2002). Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments."
  40. (1995). BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes."
  41. (1997). Basic and clinical immunology. Churchill Livingstone.
  42. (2003). Biology and treatment of chronic lymphocytic leukemia." Hematology Am Soc Hematol Educ Program:
  43. (1987). Biology of chronic lymphocytic leukemia."
  44. (2003). Bystander transfer of functional human CD40 ligand from gene-modified fibroblasts to B-chronic lymphocytic leukemia cells."
  45. (1986). Cancer after transplantation."
  46. (2002). Cancer immunotherapy using gene-modified dendritic cells."
  47. (1995). Cancer risk after renal transplantation in the Nordic countries, 1964-1986."
  48. (2002). Cancer vaccines for hematologic malignancies."
  49. (1996). Cancer vaccines: a road map for the next decade."
  50. (2005). Cancer/testis antigens, gametogenesis and cancer."
  51. (2002). Cancer/testis antigens: an expanding family of targets for cancer immunotherapy."
  52. (2002). CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease."
  53. (2004). CD40 activation: potential for specific immunotherapy in B-CLL."
  54. (1994). CD40 preferentially costimulates activation of CD4+ T lymphocytes."
  55. (1997). CD40 triggering of chronic lymphocytic leukemia B cells results in efficient alloantigen presentation and cytotoxic T lymphocyte induction by up-regulation of CD80 and CD86 costimulatory molecules."
  56. (1999). CD40-activated B-cell chronic lymphocytic leukemia cells for tumor immunotherapy: stimulation of allogeneic versus autologous T cells generates different types of effector cells."
  57. (2000). CD40-CD40 ligand."
  58. (2000). CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia."
  59. (2002). CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia."
  60. (1999). Cells and cytokines in immunotherapy and gene therapy of cancer."
  61. (1991). Cellular and humoral immune responses against cancer: implications for cancer vaccines."
  62. (2004). Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia."
  63. (1997). Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor."
  64. (1998). Characterization of human colon cancer antigens recognized by autologous antibodies."
  65. (2005). Chronic Lymphocytic Leukemia (CLL): First-Line Treatment." Hematology Am Soc Hematol Educ Program:
  66. (1998). Chronic lymphocytic leukemia B cells can express CD40 ligand and demonstrate T-cell type costimulatory capacity."
  67. (1998). Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors."
  68. (2004). Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins."
  69. (2003). Chronic lymphocytic leukemia-reactive T cells during disease progression and after autologous tumor cell vaccines."
  70. (2001). Chronic lymphocytic leukemia: case-based session." Hematology Am Soc Hematol Educ Program:
  71. (2000). Chronic lymphocytic leukemia."
  72. (2002). Chronic lymphocytic leukemia." Hematology Am Soc Hematol Educ Program:
  73. (2001). Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia."
  74. (2008). Clinical applications of natural killer T cellbased immunotherapy for cancer."
  75. (2006). Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study."
  76. (1975). Clinical staging of chronic lymphocytic leukemia."
  77. (2001). CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens."
  78. (2003). CpG motifs: the active ingredient in bacterial extracts?"
  79. (1991). Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family."
  80. (1996). Cross-linking CD40 on B cells preferentially induces stress-activated protein kinases rather than mitogen-activated protein kinases."
  81. (2004). Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens."
  82. Cross-priming of naive CD8 T cells against melanoma antigens using dendritic cells loaded with killed allogeneic melanoma cells."
  83. (2003). Current developments in cancer vaccines and cellular immunotherapy."
  84. (2004). Cytotoxic T cell induction against human malignant melanoma cells using HLA-A24-restricted melanoma peptide cocktail."
  85. (1997). Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units."
  86. (2002). Defining tumor antigens: mRNA, protein or cytotoxicity?" Trends Immunol 23(5): 236-7; author reply
  87. (2006). Dendritic cell-based cancer immunotherapy targeting MUC-1."
  88. (1998). Dendritic cells and the control of immunity."
  89. (1999). Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses."
  90. (2000). Dendritic cells in cancer immunotherapy."
  91. (2003). Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell-tumour hybrids in B-CLL."
  92. (1996). Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo."
  93. (2006). Detection and functional analysis of CD8+ T cells specific for PRAME: a target for T-cell therapy."
  94. (1996). Detection and quantification of blood-derived CD8+ T lymphocytes secreting tumor necrosis factor alpha in response to HLA-A2.1-binding melanoma and viral peptide antigens."
  95. (2002). Developmentally regulated expression of survivin in the human thymus."
  96. (1998). Differential coupling of membrane Ig and CD40 to the extracellularly regulated kinase signaling pathway."
  97. (2002). Differential expression of granulysin and perforin by NK cells in cancer patients and correlation of impaired granulysin expression with progression of cancer."
  98. (2004). Differential expression of SAP and EAT-2-binding leukocyte cell-surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4)."
  99. (2004). Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia."
  100. (2002). Differential subcellular localization of functionally divergent survivin splice variants."
  101. (2006). Directions in the immune targeting of cancer: lessons learned from the cancer-testis Ag NY-ESO-1."
  102. (2001). DNA repair initiated in chronic lymphocytic leukemia lymphocytes by 4-hydroperoxycyclophosphamide is inhibited by fludarabine and clofarabine."
  103. (2001). Does resistance to apoptosis affect clinical response to antitumor drugs?"
  104. (1989). Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells."
  105. (1998). Effect of mild acute stress on immune cell distribution and natural killer cell activity in breast cancer patients."
  106. (2003). Effects of preactivated autologous T lymphocytes on CD80, CD86 and CD95 expression by chronic lymphocytic leukemia B cells."
  107. (2002). Efficient gene transfer of CD40 ligand into primary B-CLL cells using recombinant adeno-associated virus (rAAV) vectors."
  108. (2001). Efficient identification of novel HLA-A(*)0201-presented cytotoxic T lymphocyte epitopes in the widely expressed tumor antigen PRAME by proteasome-mediated digestion analysis."
  109. (1997). Efficient induction of antitumor cytotoxic T lymphocytes from a healthy donor using HLA-A2-restricted MAGE-3 peptide in vitro."
  110. (1994). Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colonystimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha."
  111. (1994). Elevated levels of MDM-2 and p53 expression are associated with high grade non-Hodgkin's lymphomas."
  112. (2000). Emerging therapies and future directions in chronic lymphocytic leukaemia--chemotherapy."
  113. (2005). Enhancing the immunostimulatory function of dendritic cells by transfection with mRNA encoding OX40 ligand."
  114. (2005). Epigenetic treatment of hematopoietic malignancies: in vivo targets of demethylating agents."
  115. (2006). Epigenetics in chronic lymphocytic leukemia."
  116. (2001). Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation."
  117. Evaluation of role of natural killer cells in radiation-induced leukemogenesis in mice."
  118. (2000). Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia."
  119. (1997). Ex vivo generation of human anti-pre-B leukemia-specific autologous cytolytic T cells."
  120. (2001). Expression of MAGE tumour-associated antigens is inversely correlated with tumour differentiation in invasive ductal breast cancers: an immunohistochemical study."
  121. (1994). Expression of MUC1 on myeloma cells and induction of HLA-unrestricted CTL against MUC1 from a multiple myeloma patient."
  122. (2003). Expression of serologically identified tumor antigens in acute leukemias."
  123. (1998). Expression of SSX genes in human tumors."
  124. (1998). Expression of Survivin in
  125. (2002). Expression of survivin in CIN and invasive squamous cell carcinoma of uterine cervix."
  126. (2001). Expression of survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy."
  127. (2001). Expression of survivin in normal, hyperplastic, and neoplastic colonic mucosa."
  128. (2001). Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors."
  129. (1995). Expression of the MAGE gene family in human lymphocytic leukemia."
  130. (1997). Expression profile of MDM-2 proteins in chronic lymphocytic leukemia and their clinical relevance."
  131. (1995). Failure of B cells of chronic lymphocytic leukemia in presenting soluble and alloantigens."
  132. (1995). Fas-mediated cytotoxicity by freshly isolated natural killer cells."
  133. (2005). Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes."
  134. (2001). Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells."
  135. (1998). Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells."
  136. (2001). Generation in vitro of B-cell chronic lymphocytic leukaemia-proliferative and specific HLA class-II-restricted cytotoxic T-cell responses using autologous dendritic cells pulsed with tumour cell lysate."
  137. (2003). Generation of cytotoxic responses in mice and human individuals against hematological malignancies using survivin-RNA-transfected dendritic cells."
  138. (1997). Generation of dendritic cells in vitro from peripheral blood mononuclear cells with granulocyte-macrophage-colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha for use in cancer immunotherapy."
  139. (1997). Generation of peptidespecific cytotoxic T lymphocytes using allogeneic dendritic cells capable of lysing human pancreatic cancer cells."
  140. (2000). Generation of survivin-specific CD8+ T effector cells by dendritic cells pulsed with protein or selected peptides."
  141. (1999). Genes encoding tumor-specific antigens are expressed in human myeloma cells."
  142. (2005). Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene."
  143. (1990). Granulocyte-macrophage colonystimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro."
  144. (1996). Granulocyte-macrophagecolony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo."
  145. (1997). Granulysin, a new human cytolytic granuleassociated protein with possible involvement in cell-mediated cytotoxicity."
  146. (2004). Guidelines on the diagnosis and management of chronic lymphocytic leukaemia."
  147. (2003). HBXIP functions as a cofactor of survivin in apoptosis suppression."
  148. (2001). Hierarchy, Tolerance, and Dominance in the Antitumor T-Cell Response."
  149. (1999). High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals."
  150. (1990). Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping."
  151. (1985). Host resistance directed selectively against H2-deficient lymphoma variants. Analysis of the mechanism."
  152. (2001). Human inhibitor of apoptosis protein (IAP) survivin participates in regulation of chromosome segregation and mitotic exit."
  153. (2006). Human Ly9 (CD229) as novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (B-CLL) recognized by autologous CD8+ T cells."
  154. (1995). Human neoplasms elicit multiple specific immune responses in the autologous host."
  155. (2002). Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway."
  156. (2008). Human Toll like recepotor (TLR) 9 expression and function in haematological and non-haematological malignancies.
  157. (1996). Human tumor antigens recognized by T lymphocytes."
  158. (1999). IAP family proteins--suppressors of apoptosis."
  159. (1998). IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs."
  160. (1997). Identification and characterization of an IkappaB kinase."
  161. (2001). Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients."
  162. (2006). Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia."
  163. (2003). Identification of a global gene expression signature of B-chronic lymphocytic leukemia."
  164. (2004). Identification of a novel splice variant of the human anti-apoptopsis gene survivin."
  165. (2002). Identification of a novel WT1-derived peptide which induces human leucocyte antigen-A24-restricted anti-leukaemia cytotoxic T lymphocytes."
  166. (1995). Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes."
  167. (2000). Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins."
  168. (2006). Identification of HLA-A*0201-presented T cell epitopes derived from the oncofetal antigen-immature laminin receptor protein in patients with hematological malignancies."
  169. (1998). Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library."
  170. (2002). Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor."
  171. (1996). Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region."
  172. (2001). IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity."
  173. (2002). Imaging immune surveillance by T cells and NK cells."
  174. (2002). Immune complex-mediated antigen presentation induces tumor immunity."
  175. (2001). Immune responses to tumour antigens: implications for antigen specific immunotherapy of cancer."
  176. (1995). Immunocytochemical and flow cytometric detection of proteinase 3 (myeloblastin) in normal and leukaemic myeloid cells."
  177. (2000). Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies."
  178. (2001). Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues."
  179. (2004). Immunohistochemical and molecular analysis of human melanomas for expression of the human cancer-testis antigens NY-ESO-1 and LAGE-1."
  180. (2002). Immunohistochemical localization of survivin in benign cervical mucosa, cervical dysplasia, and invasive squamous cell carcinoma."
  181. (1998). Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma."
  182. (1998). Immunology. Fifth edition.
  183. (2000). Immunostimulatory CpG-oligonucleotides cause proliferation, cytokine production, and an immunogenic phenotype in chronic lymphocytic leukemia B cells."
  184. (2004). Immunotherapy of cancer: from vision to standard clinical practice."
  185. (2005). Immunotherapy via dendritic cells."
  186. (2003). In vitro dendritic cell-induced T cell responses to B cell chronic lymphocytic leukaemia enhanced by IL-15 and dendritic cell-B-CLL electrofusion hybrids."
  187. (1980). In vivo natural reactivity of mice against tumor cells."
  188. (1983). In vivo role of natural killer cells: involvement of large granular lymphocytes in the clearance of tumor cells in anti-asialo GM1-treated rats."
  189. (2001). INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow."
  190. (2003). Induction of cytotoxic T-cell responses against the oncofetal antigen-immature laminin receptor for the treatment of hematologic malignancies."
  191. (2000). Infection and immunity in chronic lymphocytic leukemia."
  192. (2003). Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase-positive cells lacking a myofibroblastic phenotype."
  193. (1998). Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer."
  194. (1999). Interleukin-12 as an adjuvant for cancer immunotherapy."
  195. (1995). Involvement of CRAF1, a relative of TRAF, in CD40 signaling."
  196. (2002). IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase."
  197. (1996). Is cancer dangerous to the immune system?"
  198. (2002). Is chronic lymphocytic leukemia one disease?"
  199. (1990). Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus."
  200. (1996). Isolation and characterization of cDNA clones for Humly9: the human homologue of mouse Ly9."
  201. (1994). Isolation of naturally processed peptides recognized by cytolytic T lymphocytes (CTL) on human melanoma cells in association with HLA-A2.1."
  202. (1997). Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells."
  203. (2000). Kuby immunology. Fourth edition.
  204. (1998). Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy."
  205. (2001). Lymphocyte-mediated immunosurveillance of epithelial cancers?"
  206. (2001). MAGE-A genes are not expressed in human leukemias."
  207. (2008). Maintenance bacillus Calmette-Guerin in high-risk nonmuscle-invasive bladder cancer: how much is enough?"
  208. (1999). Major histocompatibility complex class I restricted cytotoxic T cells specific for natural melanoma peptides recognize unidentified shared melanoma antigen(s)."
  209. (1996). Making the most of mucin: a novel target for tumor immunotherapy."
  210. (1996). Malignant melanoma in organ allograft recipients."
  211. (2006). MDM2 is recognized as a tumor-associated antigen in chronic lymphocytic leukemia by CD8+ autologous T lymphocytes."
  212. (2000). MDM2--master regulator of the p53 tumor suppressor protein."
  213. (2003). Mdm2: A regulator of cell growth and death."
  214. (1998). Mechanisms of MHC class I--restricted antigen processing."
  215. (1994). Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes."
  216. (2003). Membrane expression of proteinase 3 is genetically determined."
  217. (2003). MHC class I antigens, immune surveillance, and tumor immune escape."
  218. (1989). Model predicting survival in stage I melanoma based on tumor progression."
  219. (2006). Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis."
  220. (2005). Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor-reactive cytotoxic T lymphocytes."
  221. (2000). Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses."
  222. (2004). mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies."
  223. (2004). Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia."
  224. (1997). MyD88: an adapter that recruits IRAK to the IL-1 receptor complex."
  225. (1996). National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment."
  226. (1993). Natural killer cells induce activated murine B cells to secrete Ig."
  227. (2002). New aspects of naturalkiller-cell surveillance and therapy of cancer."
  228. (1998). New paths in human cancer serology."
  229. (2004). NK cell depletion diminish tumour-specific B cell responses."
  230. (2000). NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway."
  231. (2000). NKT cells and tumor immunity--a doubleedged sword."
  232. (2000). NKT cells: facts, functions and fallacies."
  233. (1999). NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP."
  234. (2003). Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma."
  235. (2002). Novel effects of neutrophilderived proteinase 3 and elastase on the vascular endothelium involve in vivo cleavage of NF-kappaB and proapoptotic changes in JNK, ERK, and p38 MAPK signaling pathways."
  236. (2000). Novel therapies for chronic lymphocytic leukemia in the 21st century."
  237. (2004). NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors."
  238. (1999). One hundred years of cancer immunotherapy: a critical appraisal."
  239. (2004). Peptide Based Vaccine Design for Cancer Immunotherapy." Letters
  240. (1997). Perforin-enhancing protein, a low molecular weight protein of cytotoxic lymphocyte granules, enhances perforin lysis."
  241. (2006). Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia."
  242. (1999). Pleiotropic cell-division defects and apoptosis induced by interference with survivin function."
  243. (2003). Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR."
  244. (1999). Polymorphism and evolution of HLA class I and II genes and molecules."
  245. (2005). Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules."
  246. (2005). PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects."
  247. (2007). PRAME mRNA levels in cases with chronic leukemia: Clinical importance and review of the literature."
  248. (1998). PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells."
  249. (2003). Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies."
  250. (1999). Presence of proteinase 3 in secretory vesicles: evidence of a novel, highly mobilizable intracellular pool distinct from azurophil granules."
  251. (2000). Prognostic significance of survivin expression in diffuse large B-cell lymphomas."
  252. (1996). Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma."
  253. (2001). Progress in human tumour immunology and immunotherapy."
  254. Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification."
  255. (1994). Proliferating dendritic cell progenitors in human blood."
  256. (1999). Proteases to die for."
  257. (2006). Proteinase 3 is an IL-32 binding protein."
  258. (2001). Proteinase 3, Wegener's autoantigen: from gene to antigen."
  259. (2001). Quantitative analysis of the anti-apoptotic gene survivin expression in malignant haematopoietic cells."
  260. (2001). Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia."
  261. (2005). Recent advances in immunotherapy of B-CLL using ex vivo modified dendritic cells."
  262. (2000). Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids."
  263. (2002). Regulation of microtubule stability and mitotic progression by survivin."
  264. (2001). Regulation of the immune response by antigen."
  265. (2001). Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34(+) cells by hematopoietic growth factors: implication of survivin expression in normal hematopoiesis."
  266. (2001). Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia."
  267. (2004). Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia."
  268. (1997). Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors."
  269. (2005). Responses to human CD40 ligand/human interleukin2 autologous cell vaccine in patients with B-cell chronic lymphocytic leukemia."
  270. (2000). Role of natural killer cells and T cells in immune surveillance."
  271. (2000). Selective elimination of leukemic CD34(+) progenitor cells by cytotoxic T lymphocytes specific for WT1."
  272. (1986). Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy."
  273. (1997). Serological identification of human tumor antigens."
  274. (1995). Signaling through the hematopoietic cytokine receptors."
  275. (2000). Simultaneous expression of different immunogenic antigens in acute myeloid leukemia."
  276. (1998). Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes."
  277. (2003). SLLP1, a unique, intra-acrosomal, non-bacteriolytic, c lysozyme-like protein of human spermatozoa."
  278. (2007). Specific CD8(+)T cell responses to HLA-A2 restricted MAGE-A3 p271-279 peptide in hepatocellular carcinoma patients without vaccination."
  279. (2001). Spontaneous cytotoxic T-cell responses against survivinderived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients."
  280. (1997). SSX: a multigene family with several members transcribed in normal testis and human cancer."
  281. (2000). Stem-cell transplantation for chronic lymphocytic leukemia: the 1999 perspective."
  282. (1998). Sticky and smelly issues: lessons on tumour cell and leucocyte trafficking, gene and immunotherapy of cancer."
  283. (2001). Structural basis for the inhibition of caspase-3 by XIAP."
  284. (2000). Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement."
  285. (1994). Structure, chromosomal localization, and expression of 12 genes of the MAGE family."
  286. (1986). Subcellular location and properties of bactericidal factors from human neutrophils."
  287. (2004). Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia."
  288. (2005). Survivin 2alpha: a novel Survivin splice variant expressed in human malignancies."
  289. (2003). Survivin acts as an antiapoptotic factor during the development of mouse preimplantation embryos."
  290. Survivin and aven: two distinct antiapoptotic signals in acute leukemias."
  291. (1999). Survivin apoptosis: an interloper between cell death and cell proliferation in cancer."
  292. (2005). Survivin as a target for new anticancer interventions."
  293. (2003). Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells."
  294. (2002). Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions."
  295. (2006). Survivin in esophageal cancer: An accurate prognostic marker for squamous cell carcinoma but not adenocarcinoma."
  296. (2003). Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells."
  297. (2001). Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia."
  298. (2005). Survivin splice variants regulate the balance between proliferation and cell death."
  299. (2003). Survivin- an inhibitor of apoptosis and a new therapeutic target in cancer."
  300. (2003). Survivin, versatile modulation of cell division and apoptosis in cancer."
  301. (2004). Survivin: a bifunctional inhibitor of apoptosis protein."
  302. (2001). T cells and tumours."
  303. (1994). T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and enhance their costimulatory activity."
  304. (1995). T-cell immunotherapy of tumors by adoptive transfer of cytotoxic T lymphocytes and by vaccination with minimal essential epitopes."
  305. (2002). T-cell responses against chronic lymphocytic leukemia cells: implications for immunotherapy."
  306. (1996). Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells."
  307. (2006). Targets and strategies for T-cell based vaccines in patients with B-cell chronic lymphocytic leukemia."
  308. (2004). The
  309. (2003). The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal."
  310. (2002). The alternative transcript of CD79b is overexpressed in B-CLL and inhibits signaling for apoptosis."
  311. (2000). The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent."
  312. (2000). The biochemistry of apoptosis."
  313. (2000). The CD2-subset of the Ig superfamily of cell surface molecules: receptor-ligand pairs expressed by NK cells and other immune cells."
  314. (1998). The cellular biology of B-cell chronic lymphocytic leukemia."
  315. (2003). The circulating dendritic cell compartment in patients with chronic lymphocytic leukemia is severely defective and unable to stimulate an effective T-cell response."
  316. (2004). The clinical and epidemiological burden of chronic lymphocytic leukaemia."
  317. (1990). The distinct surface of human blood dendritic cells, as observed after an improved isolation method."
  318. (2001). The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes."
  319. (2003). The expression of PRAME in chronic lymphoproliferative disorders."
  320. (2004). The frequent expression of cancer/testis antigens provides opportunities for immunotherapeutic targeting of sarcoma."
  321. (1993). The human MDM-2 oncogene is overexpressed in leukemias."
  322. (2004). The immunobiology of cancer immunosurveillance and immunoediting."
  323. (1998). The inhibitors of apoptosis (IAPs) and their emerging role in cancer."
  324. (2002). The innate immune response to tumors and its role in the induction of T-cell immunity."
  325. (1994). The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin."
  326. (2001). The molecular basis and potential role of survivin in cancer diagnosis and therapy."
  327. (2006). The origin of B-cell chronic lymphocytic leukemia."
  328. (1994). The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody repertoire."
  329. (2003). The resistance of B-CLL cells to DNA damage-induced apoptosis defined by DNA microarrays."
  330. (2001). The role of caspase-8 in resistance to cancer chemotherapy."
  331. (1999). The role of cytotoxic Tlymphocytes in the prevention and immune surveillance of tumors--lessons from normal and immunodeficient mice."
  332. (1995). The role of natural killer cells in immune surveillance of cancer."
  333. (2001). The role of survivin as a new target of diagnosis and treatment in human cancer."
  334. (2004). The spermatozoa protein, SLLP1, is a novel cancer-testis antigen in hematologic malignancies."
  335. (1996). The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40."
  336. (1996). The structure and ligand interactions of CD2: implications for T-cell function."
  337. (2001). The Survivin saga goes in vivo."
  338. (1991). The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893." Clin Orthop Relat Res(262):
  339. (1993). The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas."
  340. (2003). The use of dendritic cells in cancer immunotherapy."
  341. (1998). The Wilms' tumor 1 gene: oncogene or tumor suppressor gene?"
  342. (2002). Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study."
  343. (1998). TNF receptor-associated factor-3 signaling mediates activation of p38 and Jun N-terminal kinase, cytokine secretion, and Ig production following ligation of CD40 on human B cells."
  344. (1996). TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling."
  345. (2005). Transduction of CLL cells by CD40 ligand enhances an antigen-specific immune recognition by autologous T cells."
  346. (1992). Transfection and expression of a gene coding for a human melanoma antigen recognized by autologous cytolytic T lymphocytes."
  347. (2006). Tumor antigen expression in melanoma varies according to antigen and stage."
  348. (1999). Tumor content of the antiapoptosis molecule survivin and recurrence of bladder cancer."
  349. (2002). Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-kappa B/Rel-regulated inhibitors of apoptosis."
  350. (1998). Tumor necrosis factor receptor-associated factor 6 (TRAF6) stimulates extracellular signal-regulated kinase (ERK) activity in CD40 signaling along a ras-independent pathway."
  351. (2005). Tumor-associated antigen preferentially expressed antigen of melanoma (PRAME) induces caspase-independent cell death in vitro and reduces tumorigenicity in vivo."
  352. (1998). Tumors express both unique TSTA and crossprotective 44 kDa oncofetal antigen."
  353. (2006). Type, density, and location of immune cells within human colorectal tumors predict clinical outcome."
  354. (2001). Understanding Immunology.
  355. (2002). Universal tumor antigens as targets for immunotherapy."
  356. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia."
  357. (1998). Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells."
  358. (1996). Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells."
  359. (1999). Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma."
  360. (2003). Validating survivin as a cancer therapeutic target."
  361. (2004). Wegener granulomatosis in childhood and adolescence."
  362. (2002). What is a natural killer cell?"
  363. (2007). WT1 peptide cancer vaccine for patients with hematopoietic malignancies and solid cancers."
  364. (2001). WT1-specific serum antibodies in patients with leukemia."

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.