Utilization of gene-engineered T cells as an effective cancer immunotherapy treatment

Phillip K Darcy

: J Bioengineer & Biomedical Sci

Abstract :

Adoptive immunotherapy involving genetic modification of T cells with antigen-specific chimeric single-chain receptors is a promising approach for treatment of cancer. To determine whether gene-modified T cells could induce anti-tumor effects without associated autoimmune pathology, we assessed the ability of T cells expressing an anti-Her-2 chimeric receptor to eradicate tumor in Her-2 transgenic mice that express human Her-2 as a self-antigen in brain and mammary tissue. In adoptive transfer studies, we demonstrated significant improvement in the survival of mice bearing Her-2+ 24JK tumor following administration of anti-Her-2 T cells compared to control T cells. The incorporation of a lymphoablative step prior to adoptive transfer of anti-Her-2 T cells, and administration of IL-2 were both found to further enhance survival. The reduction in tumor growth was also correlated with localization of transferred T cells at the tumor site. Furthermore an antigen-specific recall response could be induced in long term surviving mice following rechallenge with Her-2+ tumor. Importantly, anti-tumor effects were not associated with any autoimmune pathology in normal tissue expressing Her-2 antigen. This study highlights the therapeutic potential of using gene-engineered T cells as a safe and effective treatment for cancer. We are currently assessing the therapeutic efficacy and safety of this approach in

Biography :

Phil Darcy completed his PhD in 1994 from the University of Melbourne and postdoctoral studies at St Vincents Hospital and at the Austin Research Institute. He is currently head of the Cancer Immunotherapy laboratory at the Peter MacCallum Cancer Centre. His work is focused on utilizing genetically modified T cells for specifically targeting cancer and translation of this approach into patients. He has published more than 70 papers in reputed journals in this area and has received both national and international funding to support his work.