Designer T Cells for Breast Cancer Therapy: Phase I Studies
Annual rept. 1 Jul 1999-30 Jun 2000
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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In the present report we describe studies using several types of chimeric immune receptors. These receptors consist of an antibody fragment against the CEA tumor antigen joined to signaling portions of various T cell receptors e.g., IgTCR, IgCD28, IgLFAi. The antibody fragment confers CEA specificity to the receptor, while the signaling domains transmit T cell activation and costimulation signals. These receptors allow the T cell to bypass immune tolerance to CEA and to activate effector functiones in a tumor specific manner. We describe our progress in completing a phase I study using IgTCR alone. We also present in vitro proof-of-principle studies using combinations of different receptors. These studies demonstrate that specific signaling molecules activate specific T cell effector functions in a tumor specific manner. These studies identify the key immune regulatory elements necessary to reconstructing an effective anti-tumor immune response.
- Medicine and Medical Research