ERBB2-CAR-Engineered Cytokine-Induced Killer Cells Exhibit Both CAR-Mediated and Innate Immunity Against High-Risk Rhabdomyosarcoma

Abstract

Merker et al. ERBB2-CAR-Engineered CIK Cells Against Rhabdomyosarcoma progression compared to untreated controls. ERBB2-CAR CIK cell therapy also supported innate immunity as evidenced by selective accumulation of NK and T-NK cell subpopulations in disseminated RMS tumors, which was not observed for WT CIK cells. Our data underscore the power of heterogenous immune cell populations (T, NK, and T-NK cells) to control solid tumors, which can be further enhanced with CARs, suggesting ERBB2-CAR CIK cells as a potential treatment for high-risk RMS.

Engineered NK Cells Against Cancer and Their Potential Applications Beyond

“…CAR-NK therapy has been evaluated as a therapeutic option of various solid tumors, targeting different antigens for each application. More specifically, CAR-NK cell therapy has been assessed in ovarian cancer (NKG2D ligands (NKG2DL), PSMA, FRa, CD24, HER2 or mesothelin) (113,124,(221)(222)(223)(224), glioblastoma (NKG2DL, EGFRvIII and ErbB2) (128,225,226), colorectal cancer (NKG2DL and EpCAM)124,187, prostate cancer (PSMA and NKG2DL) (128,227), hepatocellular carcinomas (c-MET, GPC3 or CD147) (70,127,228), pancreatic cancer (mesothelin and FRa) (151,229,230), high-risk myosarcoma (ErbB2) (231), gastric cancer (HER2) (170), breast cancer (ErbB2, EGFR and TF) (192,232,233), head and neck cancer (PD-L1) (234,235), neuroblastomas and melanoma (GD2) (236) and lung cancer (NKG2DL and EGFR) (128,190). Overall, these preclinical studies showed superior antitumor responses in vitro and/or in vivo compared to non-transduced or control NK cells.…”

Multipurposing CARs: Same engine, different vehicles

“…This research group also developed CD33-targeting CAR CIK cells using the SB transposon system for the treatment of acute myeloid leukemia (AML), which were significantly effective against AML and chemotherapy-resistant AML in a preclinical setting. 40 In another study, Merker et al 41 engineered ERBB2-CAR CIK cells to treat high-risk rhabdomyosarcoma. This preclinical study demonstrated that ERBB2-CAR CIK cells eradicated RH30 tumors in mice but failed to clear tumor burden in relapsed disease.…”

An Alternative Source for Allogeneic CAR T Cells With a High Safety Profile

“…Most previous studies investigated the bulk CIK cells re-engineered with a CAR structure ( 12 , 13 ). Although in vitro data have shown superior antitumor effect of unmodified CD3+CD56+ CIK cells over the CD3+CD56- counterpart in the context of non-MHC restriction ( 14 , 15 ), this difference might not be obvious when CIK cells are genetically introduced with a CAR component.…”