Antitumor T-cell Response Laboratory
Eric Tran, Ph.D., Assistant Member, Antitumor T-cell Response Laboratory
Immunotherapies that harness the T-cell response, such as interleukin-2 (IL-2), adoptive T-cell transfer, and inhibitors to the PD-1 and CTLA-4 immune checkpoint pathways, can mediate complete tumor regressions in a subset of patients with metastatic solid cancers. Accumulating evidence suggests that T cells targeting mutated antigens, which are neoantigens arising as a consequence of random somatic mutations expressed by the cancer, mediated the tumor regressions observed in some patients who received immunotherapies. The direct demonstration that T cells targeting mutated neoantigens are capable of mediating regression of metastatic epithelial cancers came from two case reports led by Eric Tran, Ph.D., during his research fellowship with Steven A. Rosenberg, M.D., Ph.D., at the National Cancer Institute, National Institutes of Health.
In these studies, published in the New England Journal of Medicine and Science, Tran et al. reported that one patient with metastatic colorectal cancer and one patient with metastatic bile duct cancer experienced objective regression of their metastatic lesions after the adoptive transfer of over 100 billion T cells targeting a unique neoantigen expressed by the patient’s own tumors. However, this therapeutic strategy has been effective only in a minority of patients and the majority of patients with metastatic epithelial cancers still do not experience durable clinical benefit with any currently available therapies. Thus, the major goal of the Antitumor T-cell Response Laboratory, led by Eric Tran, Ph.D., is to develop more effective T-cell based immunotherapies to treat patients with metastatic epithelial cancers. The Human Applications Laboratory, a core laboratory facility of the Earle A. Chiles Research Institute, is fully capable of generating personalized T-cell products for the treatment of patients with cancer on future clinical trials conducted at Providence Cancer Institute.
Learn About Dr. Tran’s Research
- Investigating the immunobiology of tumor-reactive T cells infiltrating human epithelial cancers
Tumors progress despite being infiltrated by tumor-reactive T cells. Thus, identifying the mechanisms used by tumors to impair and evade the anti-tumor T-cell response may allow for the rational development of more effective T-cell based immunotherapies that can counteract these tumor immune evasion mechanisms. The major focus of this project will be on the identification of the tumor antigens recognized by tumor-infiltrating T cells, the biological pathways disrupted by antitumor tumor-infiltrating T cells, and the genomic characteristics of the tumor cells.
- Broadening the antitumor T-cell response against human epithelial cancers
Many tumors have high genomic heterogeneity which may ultimately lead to low absent antigen expression by some cancer cells within the tumors thereby potentially limiting the efficacy of therapies that target only a small number of antigens. Thus, harnessing a T-cell response that targets a larger number of tumor antigens may counteract the extensive genomic heterogeneity found in many tumors and may lead to more effective immunotherapies against cancer. The major focus of this project will be on investigating strategies to broaden the T-cell response against multiple tumor-specific antigens.
- Enhancing T-cell function through genetic engineering
A unique aspect of T-cell transfer immunotherapy is that the T cells are harvested from the patient and cultured in the lab before ultimately being reinfused to the patient. While in the lab, genetic engineering techniques can be used to endow the T cells with properties that can potentially enhance their ability to mediate tumor destruction. The major focus of this project is to develop and evaluate novel gene engineering strategies to enhance tumor targeting and the function of T cells for adoptive immunotherapy.
View Dr. Tran’s full list of peer-reviewed publications ›