1. The Bavarian Cell Therapy Catalyst
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  3. Project 6

Project 6

Development of anti-CD28 chimeric antigen receptor (CAR) T cells

Academic Partners
Prof. Dr. med. Tobias Feuchtinger
Dr. von Haunersches Kinderspital, Klinikum der Universität München
Dr. med. Semjon Willier
Post-Doc Prof. Feuchtinger
Industry Partners
Dr. Grigory Efimov
Miltenyi B.V & Co.KG 

Prof. Dr. med. Marion Subklewe

Medizinische Klinik III, KUM

Prof. Dr. med. Michael von Bergwelt 

Medizinische Klinik III, KUM

Prof. Dr. med. Michael Hudecek 

Medizinische Klinik II, UKW

Prof. Dr. med. Hermann Einsele 

Medizinische Klinik II, UKW

Project Summary

Acute leukemia and lymphoma are the most common malignant diseases in children. About 10% are derived from the T-lineage progenitors and have an inferior prognosis compared to B-cell lineage diseases. While CAR T cells have been licensed for B-lineage leukemia and lymphoma, no CAR T cell product for T-ALL has entered clinical routine, yet. Several CAR specificities such as CD2, CD5 and CD7 are in clinical trials but challenges such as antigen escape remain.

We have previously shown that CD28 is highly expressed on T-lineage. We will exploit CD28 expression for developing CD28 CAR T cells towards a clinical phase-I trial. We have tested 20 CD28 CAR molecules and identified two lead molecules with preferential anti-leukemia functionality both in vivo and in vitro. A successful translation of CD28 CAR T cells towards clinical treatment holds great promise for patients with T-lineage leukemia.

Blaeschke, F., Stenger, D., Apfelbeck, A., Cadilha, B. L., Benmebarek, M. R., Mahdawi, J., Ortner, E., Lepenies, M., Habjan, N., Rataj, F., Willier, S., Kaeuferle, T., Majzner, R. G., Busch, D. H., Kobold, S., & Feuchtinger, T. (2021). Augmenting anti-CD19 and anti-CD22 CAR T-cell function using PD-1-CD28 checkpoint fusion proteins. Blood Cancer J, 11(6), 108. doi:10.1038/s41408-021-00499-z

Willier, S., Raedler, J., Blaeschke, F., Stenger, D., Pazos Escudero, M., Jurgeleit, F., Grünewald, T. G. P., Binder, V., Schmid, I., Albert, M. H., Wolf, A., & Feuchtinger, T. (2020). Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells. J Immunother Cancer, 8(2). doi:10.1136/jitc-2020-001052

Willier, S., Rothämel, P., Hastreiter, M., Wilhelm, J., Stenger, D., Blaeschke, F., Rohlfs, M., Kaeuferle, T., Schmid, I., Albert, M. H., Binder, V., Subklewe, M., Klein, C., & Feuchtinger, T. (2021). CLEC12A and CD33 coexpression as a preferential target for pediatric AML combinatorial immunotherapy. Blood, 137(8), 1037-1049. doi:10.1182/blood.2020006921