Oral Presentation Eradicate Cancer 2018

Generating dual-specific T cells in treating cancers (#24)

Aesha Ali 1 2 , Clare Slaney 1 2 , Bianca von Scheidt 1 2 , Jenny Westwood 1 2 , Ricky Johnstone 1 2 , Phil Darcy 1 2 , Michael Kershaw 1 2
  1. Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia

 

While immunotherapy can eliminate substantial burdens of some leukaemias, the ultimate challenge remains the eradication of large solid tumours and metastases for most cancers. In our laboratory, we generated dual-specific T cells expressing a chimeric antigen receptor (CAR) specific for Her2 and a TCR specific for the melanocyte protein (gp100). Injection of these dual specific T cells, together with recombinant vaccinia virus expressing gp100, induced durable complete remission of a variety of Her2+ tumours and established metastases, in immunocompetent mice expressing Her2 in normal tissues, including the breast and brain. To explore the translational potential for using the dual specific CAR T cell strategy, I established methods to transduce the T cells from human peripheral blood with both a TCR specific for gp100 and a CAR for Her2. From as little as 1 ml of human buffy coat, I could generate more than 109 dual-specific CAR T cells, which is sufficient for a course of treatment. The human dual-specific CAR T cells were functional in secreting IFN- and killing human cancer cells when co-cultured with the gp100 or Her2 expressing human cancer cells. The stimulation of gp100 through TCR enhanced the dual-specific CAR T cell proliferation, secretion of IFN- and killing of Her2+ human cancer cells in vitro. These characteristics were identified to be important for eradicating tumours in the mouse models. Taken together, my data provide valuable information for the development of CAR T cell therapies for patients with solid cancers. My next step is to further characterise these dual-specific T cells functions in vitro and in vivo using immunodeficient NSG mice injected with human cancer cells.