Table 3 A summary of recent reports based on CAR NK cell therapies to target EGFR positive tumor cells, in particular, HER2-overexpressing tumor cells
Cancer | Target Ag | Study model | Results | References |
|---|---|---|---|---|
Glioblastoma | EGFRvIII | In vitro In vivo | Elimination of glioblastoma cell lines by IFN-γ production Robust regression of tumor progress and considerably extended overall survival rate of the tumor-bearing mice upon intracranial infusion of NK-92-EGFR-CAR cells | |
Breast cancer | NA | In vitro In vivo | EGFR-CAR NK-92 cells and primary NK cells showed improved cytotoxicity and IFN-γ generation against MDA-MB-231, MDA-MB-468, and MCF-7 cell lines Combination therapy with EGFR-CAR NK-92 cells and oHSV-1 led to the more effective eradication of MDA-MB-231 tumor cells in mice xenografts | [188] |
Glioblastoma | EGFRvIII | In vitro | EGFRvIII -CAR NK-92 cells suppressed the proliferation and induced apoptosis in glioblastoma cell lines | [189] |
Glioblastoma | EGFRvIII | In vivo | EGFRvIII -CAR NK-92 cells modified to overexpress CXCR4 ameliorated immunotherapy of CXCL12/SDF-1α-producing U87-MG glioblastoma cell bearing mice | [190] |
Breast cancer Renal cancer | HER2 | In vitro In vivo | HER2-CAR NK-92 cells robustly lysed HER2-expressing tumor cells in vitro Selective detection and elimination of tumor cells in orthotopic breast carcinoma xenografts by HER2-CAR NK-92 cells Attenuation of pulmonary metastasis in renal cell carcinoma xenografts | [191] |
Triple-negative breast cancer (TNBC) | NA | In vitro In vivo | EGFR-CAR NK cells lysed EGFR-expressing TNBC cells in vitro EGFR-CAR NK cells suppressed both cell line-derived xenografts and patient-derived xenografts tumors in xenografts | [192] |
Real cell carcinoma (RCC) | NA | In vitro In vivo | Cabozantinib boosted the EGFR and diminished PD-L1 expression in RCC cells and eventually restored the cytotoxicity of EGFR-CAR-NK-92 cells versus the RCC cells in vitro | [193] |
Glioblastoma | EGFRvIII | In vitro | EGFRvIII-CAR NK cells showed no significant effect on tumor progression | [194] |
TNBC | HER2 | In vitro In vivo | HER2-CAR NK-92 cells improved the lysis of HER2‑expressing MDA-MB-453 and SKBr3 cell lines in vitro HER2-CAR NK-92 cells selectively decreased tumor volume and pulmonary metastasis of nude mice bearing established MDA-MB-453 cells, and also elevated the overall survival rate of the xenografts | [195] |
TNBC Ovarian cancer | HER2 | In vitro | HER2-CAR NK-92 cells selectively and proficiently eliminated established and primary HER2-expressing tumor cells in vitro | [196] |
Glioblastoma | NA | In vivo | Combination therapy with EGFR-CAR NK cells oncolytic virus expressing IL-15/IL-15Rα abrogated the proliferation and considerably improved the survival rate of mice xenografts possibly by augmented intracranial recruitment and activation of NK and CD8+ T cells | [197] |