Dye Dilution Proliferation Assay: Application of the DDPA to Identify Tumor-Specific T Cell Precursor Frequencies in Clinical Trials |
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| Authors: | Thomas Schwaab Jan L. Fisher Kenneth R. Meehan Camilo E. Fadul Alice L. Givan |
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| Affiliation: | 1. Medical Oncology Immunotherapy Program, Dartmouth Medical School, Lebanon, New Hampshire, USA;2. Concord Urology, Concord, New Hampshire, USA;3. Section of Hematology/Oncology, Dartmouth Medical School, Lebanon, New Hampshire, USA;4. Bone Marrow Transplantation Program, Dartmouth Medical School, Lebanon, New Hampshire, USA;5. Neuro-Oncology Program, Dartmouth Medical School, Lebanon, New Hampshire, USA;6. Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, USA |
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| Abstract: | A better understanding of immune effector and regulatory pathways has led to innovative, and complex, immunotherapy strategies. CD8+ cytolytic T lymphocytes (CTL) provide one common pathway of tumor cell destruction. The peripheral blood CTL compartment typically comprises a minority of anti-tumor CD8+ lymphocytes and the determination of their number during clinical trials is the focus of various laboratory methods. We have monitored tumor specific CD8+ as well as CD4+ lymphocyte precursor frequencies in the peripheral blood using a Dye Dilution Proliferation Assay (DDPA). We summarize our experience applying DDPA in a multi-parameter, antigen-specific assay, detailing some of its complexities and advantages. We provide examples of our clinical trial results showing tumor-specific CD8+ and CD4+ precursor frequency (PF) data in patients being treated on novel immunotherapy trials. |
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| Keywords: | T Cell precursor dye dilution assay immune monitoring clinical trial |
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