CCR5 predicts neurotoxicity in CAR-T-cell therapy

Ayal Rozenberg; Shahar Shelly; Raz Winer; Riva Fineman; Shani Haller; Shimrit Ringelstein-Harlev; Israel Henig; Dana Yehudai-Ofir; Tsila Zuckerman; Tamar Tadmor; Reut Harel; Esther Ganelin-Cohen; Ofrat Beyar-Katz

doi:10.1111/bjh.20228

CCR5 predicts neurotoxicity in CAR-T-cell therapy

Br J Haematol. 2025 Jun 26. doi: 10.1111/bjh.20228. Online ahead of print.

Authors

Ayal Rozenberg^{1

2}, Shahar Shelly^{1

2}, Raz Winer¹, Riva Fineman³, Shani Haller², Shimrit Ringelstein-Harlev^{3

4}, Israel Henig^{3

4}, Dana Yehudai-Ofir^{3

4}, Tsila Zuckerman^{3

4}, Tamar Tadmor^{4

5}, Reut Harel⁶, Esther Ganelin-Cohen^{7

8}, Ofrat Beyar-Katz^{3

4}

Affiliations

¹ Department of Neurology, Rambam Health Care Campus, Haifa, Israel.
² Neuroimmunology Laboratory, Ruth and Bruce Rapaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
³ Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
⁴ Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
⁵ Department of Hemathology, Bnai Zion Medical Center, Haifa, Israel.
⁶ Department of Hemathology, Emek Medical Center, Afula, Israel.
⁷ Neuroimmunological Clinic, Institute of Pediatric Neurology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
⁸ The Gray Faculty of Medical and Health Sciences Tel Aviv University, Tel Aviv, Israel.

PMID: 40572013
DOI: 10.1111/bjh.20228

Abstract

Patients undergoing chimeric antigen receptor T (CAR T)-cell therapy are at risk of developing immune effector cell-associated neurotoxicity syndrome (ICANS). We observed an upregulation of CCR5 and CCR2 expression in CD4+ T cells among patients who developed ICANS. Notably, increased CCR5 expression was detectable as early as day one post-infusion, but only in those who eventually developed ICANS, suggesting a potential role for CCR5 as an early biomarker for ICANS onset.

Keywords: CAR‐T cells; ICANS; chemokines; lymphomas; macrophages.