Balke-Want, Hyatt - CAP 36
T cell and Genome Engineering
Dr. Hyatt Balke-Want
Dept. I for Internal Medicine | University Hospital Cologne
Junior Research Group Leader
CMMC - PI - CAP 36
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Dept. I for Internal Medicine | University Hospital Cologne
Kerpener Str. 62
50937 Köln
Introduction
CAR T cells (CARTs) have heralded a new era in medicine and are showcasing the power of synthetic immunoreceptors to redirect a T cell response toward a target of interest. In B-NHL CD19 CARTs have transformed the therapeutic landscape and are now standard of care for relapsed/refractory (r/r) disease. Here, long-term data indicates durable response in nearly one third of treated patients. Resistance in the other two-thirds of B-NHL have been linked to antigen-loss, T-cell exhaustion and a T-cell suppressive TME, which induces exhaustion of CARTs.
Figure 1
Aims
We want to improve CART therapy by overcoming the suppressive tumor microenvironment in B-NHL and identify mechanisms to prevent exhaustion in CART products. To this end, we apply synthetic biology and CRISPR-based engineering. Importantly, our approach is guided by insights gained from high-dimensional profiling of relevant patient samples.
Clinical Relevance
Our work is highly relevant for clinical translation for mainly two reasons: 1) We aim to improve existing CART therapies for B-NHL and translate our insights to other malignant disease. 2) We have developed non-viral strategies to manufacture CARTs utilizing the CRISPR/Cas9 system, which bear the potential to overcome current limitations arising from limited access to GMP grade viral vector. Moreover, we and others have shown that non-viral engineering via CRISPR/Cas9 allows to edit functionally relevant loci and facilitates insertion of large therapeutic transgenes to boost CART therapy.
Lab Website
For more information, please visit the following page: T-cell and Genome Engineering Lab
Affiliations
Publications generated from 1/2025 on with CMMC affiliations
2025
- Stahl D, Gödel P, Balke-Want H, Gholamipoorfard R, Segbers P, Tetenborg L, Koker M, Dörr J, Gregor L, Bachurski D, Rose F, Simon AG, Good Z, Jakob J, Häupl B, Nill M, Flümann R, Riet T, Lange D, Blakemore SJ, Baurmann H, Voltin CA, Potter N, Schlözer L, Freihammer M, Wagener-Ryczek S, Iuga AI, Heger JM, Ludwig H, Schleifenbaum JK, Propp J, Bröckelmann PJ, Jachimowicz RD, Knittel G, Borchmann S, Merkelbach-Bruse S, Pallasch C, Peifer M, Rybniker J, Quaas A, Nitz M, Brägelmann J, Müller W, Persigehl T, Bozek K, Theobald SJ, Büttner R, Oellerich T, Hallek M, Kobold S, Chmielewski M, Reinhardt HC, Mackall C, Abedpour N, Borchmann P, Ullrich RT. CSF1R+ myeloid-monocytic cells drive CAR-T cell resistance in aggressive B cell lymphoma. Cancer Cell. 2025 Aug 11;43(8):1476-1494.e10. doi: 10.1016/j.ccell.2025.05.013. Epub 2025 Jun 12. PMID: 40513575.