Tumor Specific CD4+ T-Cell Costimulation Through a Novel Receptor Ligand Interaction.
Abstract
CD4+ T cells specific for tumor antigens have been less well characterized than CD8+ T cells. There appears to be two main reasons for this discrepancy; (1) CD8(+) T cells isolated from tumor (tumor infiltrating lymphocytes; TIL) preferentially expand in the presence of anti-CD3 and IL-2, and (2) CD4(+) T cells isolated from a tumor environment appear to be defective in signaling and therefore may not have the capacity to proliferate to tumor/tumor-associated Ag. We will attempt bypass these limitations by using a novel approach to costimulate a tumor specific CD4(+) T cell memory response. Recently, we found that CD4(+) T cells isolated near the tumor sites of patients with melanoma and head and neck cancer expressed the OX-40 receptor, but not cells in the periphery of these same patients. It is our hypothesis that these OX-40(+) T cells were recently activated in vivo in response to tumor antigens. If a costimulatory signal could be provided to these OX-40(+) T cells by the OX-40 ligand, then clonal expansion of CD4(+) T cells specific tumor should occur. In this proposal we will characterize OX-40 expression by human and mouse CD4(+) T cells specific for breast cancer and attempt to expand them both in vivo and in vitro with MHC II(+) tumors transfected with the OX-40 ligand, in essence making the tumor an antigen presenting cell capable of priming CD4 T cell immunity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADA359629
Entities
People
- Andrew D. Weinberg