Abstract MS01-2: Artificial receptors and the cellular therapy of breast cancer

Abstract

Abstract It is clear that targeting therapy to the specific molecular lesions of breast cancer affords the best opportunity to obtain effective treatment without adverse effects on normal tissues. The immune system remains one of the most effective targeting systems known, and tumor-directed monoclonal antibodies have already shown significant success in treating this and other malignant disorders. Cellular therapies based on T lymphocytes, by contrast, have not yet made an equivalent impact, even though T cell-based immune responses to tumor have many unique characteristics that should make them highly effective. In this presentation I will discuss one historic success story for cellular immunotherapy -the treatment of EBV-associated lymphoid and epithelial malignancies by tumor specific T cells -and show how the lessons learned from analyzing the mechanisms underlying this success can be implemented to treat other solid tumors including breast cancer Four components are required for effective activity;-. 1) The infused T cells must target strong and unique antigens, presented with ample accessory signals and co-stimulation; 2) The T cells should contain a polyclonal and multispecific memory population directed to tumor; 3) The T cells must be able to overcome potent immune escape mechanisms 4) The environment should favor (homeostatic) lymphoid expansion. We and others are developing a systematic approach to meet these requirements by introducing novel artificial receptors (Chimeric Antigen Receptors – CARs) and other cell engineering components into T lymphocytes. As an increasing level of success becomes documented in hematological malignancy and solid tumors, we can be hopeful that these therapies will become part of the standard of care for breast cancer as well. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr MS01-2.