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Current Research Projects

Project Title T cell gene therapy to eradicate disseminated breast cancers

Researcher: Richard Junghans, PhD, MD, Associate Professor of Medicine, Boston University School of Medicine, and Roger Williams Medical Center, Providence, Rhode Island at Boston University School of Medicine and Roger Williams Medical Center, Providence, Rhode Island

Study Abstract: Background: Our research group has created chimeric immune receptors (CIR) that in their simplest form are immunoglobulin-T cell receptors (IgTCR), i.e., molecular fusion products of single chain antibody (Ab) binding domains with the ζ signaling chain of the TCR that provides Signal 1. When expressed by gene therapy techniques in recipient T cells, the resulting “designer T cells” combine the specificity of Ab with the cytotoxic potency of T cells in a new type of immune therapy against breast and other cancers. We previously conducted a clinical trial under prior DOD and NCI funding that showed activity against breast and colon tumors in vivo with patients’ designer T cells, but that the effect was short lived via a process of activation-induced cell death (AICD). We modified these T cells to incorporate CD28 co-stimulation on antigen contact in order to oppose AICD and secure an intratumoral T cell expansion and extended in vivo effect. For this work, we are exploiting CEA, which is the 2nd most prevalent tumor antigen on breast cancers, on 30-60% of metastatic cases, accounting for 12-25,000 breast cancer deaths per year. CEA is also the only breast cancer antigen shown to be safely targeted with designer T cells in human studies and for which advanced generation designer T cells have been prepared and for which there is an active IND. With this antigen platform, benefits to a large number of patients via this modality are promised in a faster time frame than with any other breast cancer antigen.

Hypotheses: that designer T cells offer an immune based alternative to cancer therapies that has the potential to cure metastatic breast cancers; that several components will potentially contribute to an optimal therapeutic anti-tumor agent; that CEA is the optimal platform for a rapid optimization that will allow generalizable lessons over the range of breast cancer antigens.

Specific Aims:
Clinical (existing products):
1. To test efficacy of 2nd gen designer T cells in metastatic breast cancer
2. To test ancillary procedures for improved persistence and activity of infused designer T cells
Advanced Research & Development:
3. To create and test other CIR designs with alternative co-stimulatory domains
4. To create and test CIR with to avoid need for IL2 supplementation in vivo to sustain T cell survival
Clinical (new products):
5. To conduct clinical trials with the new generation products.