Adoptive T-Cell Therapy
Development of innovative paradigms beyond vaccines is needed to safely and effectively treat patients with advanced, bulky tumor metastases. While a vaccine relies on a patient's immune system to create an antigen-specific immune response, adoptive cell therapy (ACT) using engineered T cells offers unique advantages. Specifically, tolerance removes antigen-specific T cells during their maturation, limiting the number and the potency of T cells that escape tolerance and can be harnessed by vaccination. In contrast, T cells can be engineered and expanded ex vivo to produce large numbers of cells expressing receptors of high affinity, maximizing their potency. Importantly, we have shown that while GUCY2C vaccines possess antitumor activity, they are limited by tolerance, reducing their efficacy against large, established tumors. In mouse models, GUCY2C-targeted ACT is superior to GUCY2C-targeted vaccines in the context of established tumors. Similar techniques also have produced remarkable clinical successes in melanoma, neuroblastoma, and leukemia, but ACT approaches for adenocarcinomas remain undefined. Currently, we are interested in identifying antigen-targeted ACT approaches which can be translated to patients with metastatic disease originating in mucosal tumors. Preclinical studies have shown promising results with GUCY2C CAR-T cell therapy and we are working towards clinical trials with this approach.
Tumor recognition by T-cell receptors
Tumor recognition by chimeric antigen receptors