Hinrich Abken - B 1

Metabolic addiction and reprogramming of an anti-tumor T cell response

Abstract

Recent advances in cancer immunotherapy impressively demonstrated that a specific T cell response can control cancer in the long-term. A comprising approach is redirecting T cells by a chimeric antigen receptor (CAR) against cancer cells. Despite clinical success in treating hematologic malignancies, the mechanisms in determining the T cell response and immunological memory remain largely undefined. Emerging data indicate that costimulation in addition to the primary TCR modifies bioenergetics and metabolic signature, e.g., 4-1BB promotes respiratory capacities, mitochondrial biogenesis, and central memory development while CD28 enhances aerobic glycolysis and effector T cell maturation.
The key metabolic processes required for an efficacious T cell anti-tumor response are not identified, however, are central modulators when activated T cells with high glucose consumption need to act in the hostile tumor tissue which is heavily polarized through the Warburg effect and other anaerobic processes. We will address whether the metabolic T cell addiction is fixed or altered by higher order co-signals. From the therapeutic perspective, genetic engineering of T cells with key enzymes and/or receptor-transporter molecules will provide us with strategies to sharpen the T cell anti-tumor response in a predicted fashion.
The approach as a whole is of both basic and clinical relevance as it elucidates the link between metabolic addiction and immune response and aims to modify the T cell metabolic program into a more favourite and enduring one against cancer.

Clinical/medical relevance and sustainability in disease understanding

The spectacular success of chimeric antigen receptor (CAR) T cells in treating hematologic malignancies opens new ways in cancer therapy; the impact of metabolic reprogramming within the tumor tissue on the T cell anti-tumor response remains unclear. We here address how costimulation mediated metabolic reprogramming alters T cell physiology, persistence and anti-tumor response and whether this can be used to improve the T cell response towards an enduring control of malignant diseases.


Prof. Dr. med. Hinrich Abken

Dept. I of Internal Medicine

Prof. Dr. med. Hinrich Abken

Principal Investigator B 1
Head - Cell Sorting Facility

hinrich.abken@uk-koeln.de

Work +49 221 478 89614

Fax (Work) +49 221 478 97295

CMMC-Research Building
Robert-Koch-Str. 21
50931 Cologne

http://innere1.uk-koeln.de/profil/hinrich_abken

Publications - Hinrich Abken

Link to PubMed

Group Members

Markus Chmielewski (Post Doc)
Astrid Holzinger (Post Doc)
Andreas Hombach (Post Doc)
Johannes Kühle (Post Doc)
Tobias Riet (Post Doc)
Dorottya Horváth (PhD student)
Jennifer Makalowski (PhD student)
Viktória Golumba-Nagy (PhD student)
Lisa Hannappel (PhD student)
Danuta Chrobok (Technician)
Nicole Riet (Technician)
Petra Hofmann (Technician)
Birgit Hops (Technician)