Breast Cancer

Biography

Biography: Phillip K. Darcy

Abstract

Adoptive immunotherapy involving genetic modification of T cells with chimeric antigen receptors (CAR’s) is a promising approach for treatment of cancer although has resulted in on target toxicity in some trials. To explore this more fully, we utilized a self-antigen mouse model that expresses human Her-2 as a self-antigen in brain and mammary tissue to assess the ability of T cells expressing an anti-Her-2 chimeric receptor to eradicate Her-2+ tumor. In adoptive transfer studies, we demonstrated significant improvement in the survival of mice bearing Her-2+ tumor following administration of anti-Her-2 T cells compared to control T cells. Importantly, anti-tumor effects were not associated with any autoimmune pathology in normal tissue expressing Her-2 antigen. The reduction in tumor growth correlated with localization of transferred T cells at the tumor site and an antigen-specific recall response could be induced in long term surviving mice following rechallenge with Her-2+ tumor. In further studies we have also utilized gene-engineered T cells in combination with other immune-based therapies such as anti-PD1 which resulted in significantly enhancing therapeutic effects in mice. We have recently completed a Phase I clinical trial in patients with acute myeloid leukaemia targeting the Lewis Y carbohydrate antigen and demonstrated that the therapy was well tolerated.