35 research outputs found
Control leukemia by inducing anti-cancer immune reactivity in vivo? Potential of a dc-triggered mechanism [Poster]
Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors
BACKGROUND: Adoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications. METHODS: We provide results of a personalized T-cell manufacturing program evaluating donor, patient, T-cell product and outcome data. Patient-tailored clinical-grade EBV-specific cytotoxic T-lymphocyte (EBV-CTL) products from stem cell donors (SCD), related third party donors (TPD) or unrelated TPD from the allogeneic T-cell donor registry (alloCELL) established at Hannover Medical School were manufactured by immunomagnetic selection using CliniMACS Plus or Prodigy device and EBV PepTivators EBNA-1 and Select. Consecutive manufacturing processes were evaluated and patient outcome and side effects were retrieved by retrospective chart analysis. RESULTS: Forty clinical-grade EBV-CTL products from SCDs, related or unrelated TPDs were generated for 37 patients with and without transplantation (Tx) history within 5 days (median) after donor identification. 34 patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to complete response in 20 of 29 patients who were evaluated for clinical response. No infusion-related toxicity was reported. EBV-specific T cells in patients' blood were detectable in 16/18 monitored patients (89 %) after transfer and correlated with clinical response. CONCLUSION: In conclusion, personalized clinical-grade manufacturing of EBV-CTL products via immunomagnetic selection from SCD, related or unrelated TPD is feasible in a timely manner. Overall, EBV-CTL were clinically effective and well-tolerated. Our data suggest EBV-CTL as promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT as well as patients with pre-existing organ dysfunction
Immune modulation of AML-blasts in therapy-refractory AML-patient in vivo with clinically approved response modifiers improves clinical status, blood cell regeneration and gives rise to leukemia specific adaptive and innate immune reactive cells
Increased detection of (leukemiaspecific) adaptive and innate immune-reactive cells under treatment of AML-diseased rats and one therapy-refractory AML-patient with blastmodulating, clinically approved response modifiers
Variances in Antiviral Memory T-Cell Repertoire of CD45RA- and CD62L-Depleted Lymphocyte Products Reflect the Need of Individual T-Cell Selection Strategies to Reduce the Risk of GvHD while Preserving Antiviral Immunity in Adoptive T-Cell Therapy
Introduction!#!Viral infections and reactivations still remain a cause of morbidity and mortality after hematopoietic stem cell transplantation due to immunodeficiency and immunosuppression. Transfer of unmanipulated donor-derived lymphocytes (DLI) represents a promising strategy for improving cellular immunity but carries the risk of graft versus host disease (GvHD). Depleting alloreactive naĂŻve T cells (T!##!Methods!#!T-cell responses against ppEBV_EBNA1, ppEBV_Consensus and ppAdV_Hexon within T!##!Results!#!According to differences in the phenotype composition, antigen-specific T-cell responses in CD45RA!##!Conclusion!#!Taken together, our results indicate that CD45RA depletion is a more suitable strategy for generating