Journal Article

DKFZ-2026-01135

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Development of CAR NK Cell Lines Selectively Targeting Cancer Cells Expressing Membrane Hsp70.

Hachani, K. ; Yazdi, M. ; Carcopino, C. ; Khademi Moghadam, F. ; Smith, M. D. ; Trill, A. ; Trefny, M. P. ; Hasanzadeh Kafshgari, M. ; Hoch, C. C. ; Gaballa, A.DKFZ* ; Alkotub, B. ; Altomonte, J. ; Pockley, A. G. ; Wagner, E. ; Wollenberg, B. ; Kobold, S.DKFZ* ; Multhoff, G. ; Bashiri Dezfouli, A.

2026
Wiley Hoboken, NJ

Abstract: An effective chimeric antigen receptor (CAR)-based immunotherapy depends on both a suitable immune cell platform and a tumor-specific antigen to overcome barriers in solid tumors. Natural killer (NK) cell lines are promising platforms for CAR constructs due to their inherent tumor-killing ability, safety profile, and feasibility for standardized, off-the-shelf therapeutic use. Herein, four human NK cell lines (YT, KHYG1, NKL, and NK92) were retrovirally transduced with an anti-Hsp70 CAR targeting membrane-bound heat shock protein 70 (mHsp70), a tumor-specific antigen with broad expression on many solid tumors, but not normal cells. Computational modeling suggested a strong binding between the CAR and the extracellular domain of mHsp70. Although all NK cell lines exhibited successful CAR integration and surface expression, only NKL and NK92 cells maintained stable CAR expression and long-term viability. The anti-Hsp70 CAR NKL and NK92 cells demonstrated enhanced expression of activation markers and secretion of cytotoxic effector molecules, and robust target-specific killing of mHsp70-positive cancer cells, while sparing mHsp70-negative targets. Our findings validate the therapeutic potential of anti-Hsp70 CAR NK cells and the suitability of NKL and NK92 cells for advancing off-the-shelf CAR NK cell therapies, thereby offering a promising strategy for targeting a broad range of solid tumors expressing mHsp70.

Keyword(s): anti‐Hsp70 CAR NK cells ; head and neck squamous cell carcinoma ; immunotherapy ; membrane‐bound Hsp70 ; tumor‐associated antigen

Note: #DKTKZFB26#

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)
2. DKTK MU Translationale Krebsforschung (MU05)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DEAL Wiley ; DOAJ Seal ; Emerging Sources Citation Index ; Fees ; SCOPUS ; Web of Science Core Collection

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