Kuo-Hsiang Chuang
Taipei Medical University, Taiwan
Title: One-step mixing with anti-tumor/anti-CD3 bispecific antibody enhances tumor targeting and therapeutic efficacy of ex vivo expanded T cells
Biography
Biography: Kuo-Hsiang Chuang
Abstract
Adoptive T cell transfer, involving the ex vivo expansion of cancer patient’s T cells and then intravenous injection back to the patient, can effectively mediate tumor regression and extend patient’s life. However, lack of tumor specificity of most expanded T cells and time-consuming of generating tumor-specific T cells severely restrict in vivo survival time and anti-cancer ability of these ex vivo expanded T cells. In this study, we developed bispecific antibodies (BsAbs) by fusing an anti-CD3 scFv to the C-terminus of a Fab against tumor-associated antigen, such as EGFR or PSMA, to form α-tumor/α-CD3 BsAbs. The anti-CD3 end of the BsAb could non-covalently bind to CD3+ T cells and the anti-tumor end of BsAb can endow T cells with specificity to EGFR+ or PSMA+ tumor cells. One-step mixing with BsAbs significantly enhanced the killing efficacy of CD3+ T cells against EGFR+ colon cancer cells and PSMA+ prostate cancer cells in vitro and in vivo. Contact of BsAb-armed T cells with EGFR+ or PSMA+ tumor cells dramatically increase the release of cytotoxic factors, including: perforin, granzyme, INF-γ, and TNF-α, from these T cells to kill tumor cells. The α-tumor/α-CD3 BsAbs offer a simple one-step method to confer tumor specificity to CD3+ T cells for enhanced tumor targeting and improved therapeutic efficacy.
