Harnessing T-Cell Immunotherapy: The Development and Potential of MGD007 in Metastatic Colorectal Cancer Treatment

The abstract discusses the development and testing of a new therapy for colorectal cancer, focusing on the use of T-cells to target cancer cells. MGD007, a Dual-Affinity Re-Targeting (DART) protein, is highlighted as a promising agent designed to redirect T-cells towards colon cancer cells expressing gpA33. The protein was engineered with improved pharmacokinetic properties, including the ability to cross-react with non-human primates, facilitating preclinical studies.

The protein was produced in CHO cells and purified using standard methods. In vitro studies showed that MGD007 effectively bound to gpA33-positive cancer cells and induced T-cell-mediated lysis, without affecting gpA33-negative cells. Both human and monkey T-cells were activated and expanded in response to gpA33 expression, with no cytokine activation observed in the absence of gpA33.

In vivo studies using NOD-SCID mice implanted with Colo205 cells and human T-cells demonstrated tumor growth inhibition at low doses of MGD007. The protein was well-tolerated in cynomolgus monkeys, with pharmacokinetics indicating a prolonged presence consistent with Fc-containing molecules.

The findings suggest that MGD007 could be a potential novel treatment for colorectal cancer, with its efficacy supported by its mechanism of action and favorable pharmacokinetic profile in monkeys. The study was presented at the 105th Annual Meeting of the American Association for Cancer Research by Paul A. Moore and colleagues.