Conflicts of interest in translational research

Translational research requires a team approach to scientific inquiry and product development. Translational research teams consist of basic and clinical scientists who can be members of both academic and industrial communities. The conception, pre-clinical testing, and clinical evaluation of a diagnostic or therapeutic approach demands an intense interaction between investigators with diverse backgrounds. As the barriers between industry and academia are removed, issues of potential conflict of interest become more complex. Translational researchers must become aware of the situations which constitute conflict of interest and understand how such conflicts can impact their research programs. Finally, the translational research community must participate in the dialogue ongoing in the public and private sectors and help shape the rules that will govern conflicts that arise during the evolution of their research programs

His-tag ELISA for the detection of humoral tumor-specific immunity

<p>Abstract</p> <p>Background</p> <p>The application of high throughput molecular techniques such as SEREX are resulting in the identification of a multitude of tumor associated antigens. As newly identified antigens are incorporated into a variety of clinical trials, standardization of immunologic monitoring methods becomes increasingly important. We questioned whether mammalian cell expression of a histadine-linked human protein could be used to produce antigen suitable for detecting tumor-specific humoral immunity and whether such an assay could be amenable to standardization for clinical use.</p> <p>Methods</p> <p>We designed a his-tagged capture ELISA based on lysate from genetically engineered CHO cells for detection of antibodies to insulin-like growth factor binding protein 2, a novel tumor antigen. We performed technical and preliminary clinical validation studies, including comparison to a standard indirect ELISA based on commercially prepared recombinant antigen.</p> <p>Results</p> <p>The his-tagged capture ELISA could be standardized. Precision experiments resulted in CVs < 15%. Linearity and calibration experiments demonstrated r²values of 0.99. In comparison to Western blot analysis, his-tag and indirect ELISA accurately identified 88% and 93% of samples, respectively. Sample concordance between capture and indirect assays was highly significant (p = 0.003). Furthermore, significantly greater levels of IGFBP-2 antibody immunity were found in cancer patients compared to normal controls (p = 0.008).</p> <p>Conclusion</p> <p>A genetically engineered cell lysate based ELISA can be amenable to standardization and can detect increased levels of antibody immunity to tumor-associated antigen in cancer patients compared to non tumor-bearing healthy controls.</p

Sensitivity and specificity of tritiated thymidine incorporation and ELISPOT assays in identifying antigen specific T cell immune responses

<p>Abstract</p> <p>Background</p> <p>Standardization of cell-based immunologic monitoring is becoming increasingly important as methods for measuring cellular immunity become more complex. We assessed the ability of two commonly used cell-based assays, tritiated thymidine incorporation (proliferation) and IFN-gamma ELISPOT, to predict T cell responses to HER-2/neu, tetanus toxoid (tt), and cytomegalovirus (CMV) antigens. These antigens were determined to be low (HER-2/neu), moderate (tt), and robustly (CMV) immunogenic proteins. Samples from 27 Stage II, III, and IV HER-2/neu positive breast cancer patients, vaccinated against the HER-2/neu protein and tt, were analyzed by tritiated thymidine incorporation and IFN-gamma ELISPOT for T cell response.</p> <p>Results</p> <p>Linear regression analysis indicates that both stimulation index (SI) (p = 0.011) and IFN-gamma secreting precursor frequency (p < 0.001) are significant indicators of antigen specific immunity. ROC curves plotted to assess the performance of tritiated thymidine incorporation and the ELISPOT assay indicate that SI is a significant indicator of low T cell response to the HER-2/neu vaccine (p = 0.05), and of moderate and robust responses to tt (p = 0.01) and CMV (p = 0.016), respectively. IFN-gamma precursor frequency is a significant indicator of a robust T cell response to CMV (p = 0.03), but not of moderate tt (p = 0.09), or low HER-2/neu (p = 0.09) T cell responses.</p> <p>Conclusion</p> <p>These data underscore the importance of taking into consideration the performance characteristics of assays used to measure T cell immunity. This consideration is particularly necessary when determining which method to utilize for assessing responses to immunotherapeutic manipulations in cancer patients.</p

Immuno-Oncology biomarkers 2010 and beyond: Perspectives from the iSBTc/SITC biomarker task force

The International Society for Biological Therapy of Cancer (iSBTc, recently renamed the Society for Immunotherapy of Cancer, SITC) hosted a one-day symposium at the National Institutes of Health on September 30, 2010 to address development and application of biomarkers in cancer immunotherapy. The symposium, titled Immuno-Oncology Biomarkers 2010 and Beyond: Perspectives from the iSBTc/SITC Biomarker Task Force, gathered approximately 230 investigators equally from academia, industry and governmental/regulatory agencies from around the globe for panel discussions and presentations on the following topics: 1) immunologic monitoring: standardization and validation of assays; 2) correlation of immunity to biologic activity, clinical response and potency assays; 3) novel methodologies for assessing the immune landscape: clinical utility of novel technologies; and 4) recommendations on incorporation of biomarkers into the clinical arena. The presentations are summarized in this report; additional program information and slides are available online at the iSBTc/SITC website