Designer T-Cells for Breast Cancer Therapy: Phase I Studies
Abstract
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 isolating/expanding 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA390706
Entities
People
- Richard P. Junghans
Organizations
- Beth Israel Deaconess Medical Center