Of CARs and TRUCKs: how redirected T cell therapy can activate an innate immune cell response against cancer

Datum

12.01.2017

Zeit

14:30 - 15:30

Sprecher

Prof. Hinrich Abken

Zugehörigkeit

Zentrum für Molekulare Medizin Köln, Universitat zu Köln

Serie

IMB - Seminar

Sprache

en

Hauptthema

Biologie

Andere Themen

Biologie, Medizin

Host

IMB

Beschreibung

Adoptive therapy with CAR engineered T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, cancer cells which lack the cognate antigen are invisible to CAR T cells; those cancer cells may contribute to deadly tumor relapses. We discuss the fourth generation of CAR T cells, so called TRUCKs, which release inducible IL-12 upon CAR engagement in the targeted tumor lesion. Locally accumulating IL-12 in turn attracts an innate immune cell response towards those cancer cells that are invisible to CAR T cells. Elimination of antigen-loss tumor cells was accompanied by the accumulation of activated macrophages through a TNF-alpha mediated process. The locally restricted deposit of IL-12 by CAR T cells has the advantage to target otherwise not accessible tumor lesions, to achieve therapeutic levels in the targeted lesion, to reduce systemic toxicity and to recruit and activate innate immune cells. The strategy combines antigen-redirected immunotherapy with an antigen-independent anti-tumor response. Other cytokines may also be delivered. We discuss the potential benefit in combining cytokines, the major consequences for future strategies the immune therapy of malignant diseases and other applications of TRUCKs as targeted living factories.

Letztmalig verändert: 19.12.2016, 16:23:47