Designer T-Cells for Breast Cancer Therapy: Phase I Studies
Annual rept. 1 Jul 1998-30 Jun 1999
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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IgTCR-Modified T Cells for Breast Cancer Therapy Phase I Studies. T cells are capable of penetrating any biologic space and eliminating cells displaying foreign antigens. We have used a chimeric IgTCR molecule to create T cells with antigen-specificity directed against the CEA tumor antigen. In the present study we have examined the toxicity and tolerability of autologous T cells modified with this receptor in CEA breast cancer patients. Patients have tolerated the treatment well, and no adverse events could be attributed to the therapy. Preliminary efficacy data suggest that IgTCR-modified T cells may have some anti-tumor activity in vivo, but are limited by poor circulation after infusion. Research aimed at improving circulation have focused on isolatingexpanding subpopulations of T cells with a memory cell-like phenotype. These cells enter a resting state when deprived of IL2 rather than a apoptosis pathway. These memory-like cells may persist and circulate much better than standard ex vivo expanded cells. We have also shown that CD28 co-stimulation signals are required to induce proliferation of IgTCR T cells. Incorporating antigen-driven T cell proliferation into the activation pathway should allow any T cells that do infiltrate tumor to proliferate rapidly to high numbers. Together, these results suggest that IgTCR-modified autologous T cells may become an important modality for the treatment of metastatic breast cancer.
- Medicine and Medical Research