title: Dye dilution proliferation assay: application of the DDPA to identify tumor-specific T cell precursor frequencies in clinical trials.
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.
authors.affiliation: Medical Oncology Immunotherapy Program, Dartmouth Medical School, Lebanon, New Hampshire, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwaab
authors.forename: Jan L
authors.initials: JL
authors.lastname: Fisher
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Meehan
authors.forename: Camilo E
authors.initials: CE
authors.lastname: Fadul
authors.forename: Alice L
authors.initials: AL
authors.lastname: Givan
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
mesh_terms: D001681:Biological Assay; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002986:Clinical Trials as Topic; D004396:Coloring Agents; D006801:Humans; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology / Q000378:metabolism*
chemical_list: D004396:Coloring Agents