A novel non-HLA-restricted cellular immune assay for monitoring patient (pt) response to targeted immunotherapeutics
| Autor: | T. Schuetz, John Marshall, Howard L. Kaufman, K. E. Dolan, Kelledy Manson, G. P. Mazzara |
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| Rok vydání: | 2006 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 24:2567-2567 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 2567 Background: Many therapeutic cancer vaccines are designed to elicit T-cell immunity. In vitro monitoring of pt response is limited by the HLA-restriction of ELISPOT assays. We report a novel, non-restricted assay for measuring immune responses generated by PANVAC-VF, which comprises 2 recombinant viral vectors in a heterologous prime-boost immunization regimen. Each vector contains genes encoding the tumor antigens CEA and MUC-1, and 3 immunologic costimulatory molecules B7.1, LFA-3, and ICAM-1. The safety of PANVAC-VF was tested in a Phase 1 study of 10 pts with advanced pancreatic cancer (ASCO 2005 abstr 2576). Methods: Peripheral blood mononuclear cells (PBMCs) were drawn at baseline and each subsequent timepoint (∼2 wks after each injection) to measure cellular immune responses. PBMCs were separated from whole blood over a Ficoll gradient; isolated PBMCs were frozen in liquid nitrogen until analysis. A monkey breast cancer cell line (CMMT 110/C1) was infected with PANVAC-F or control fowlpox recombinant. On Day 2, PBMCs were incubated 10:1 with infected CMMT 110/C1 cells, and the mixtures co-cultivated for 72 h. Supernatants were assayed for interferon γ production. Results: Of 8 pts with PBMCs sufficient for testing, 5 developed an antigen-specific immune response to CEA and/or MUC-1. In general, interferon γ production steadily increased with repeat boosting immunizations. Cellular depletion experiments suggest that the result is dependent on CD4+ cells, allowing analysis of samples from all pts, unlike the ELISPOT, which is restricted to HLA-A2 peptide presentation. Preliminary analysis suggests a positive correlation of immune response with overall survival. Conclusions: We developed a novel, non-restricted cellular assay to assess immune response to a targeted immunotherapeutic, PANVAC-VF. Five of 8 assayed pts developed an antigen-specific cellular immune response. Pt numbers are small, but there appears to be a correlation between immune response and overall survival. This assay will be used for samples from a randomized Phase 3 study in pancreatic cancer and a randomized Phase 2 study in prostate cancer, generating a large data set of immune responses from all pts. [Table: see text] |
| Databáze: | OpenAIRE |
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