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Table 2 A summary of recent reports based on CAR T cell therapies to target EGFR positive tumor cells, in particular, HER2-overexpressing tumor cells

From: Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress

Cancer

Target Ag

Study model

Results

References

Triple-negative breast cancer (TNBC)

HER1

HER2

In vitro

In vivo

Induction of HS578T, MDA-MB-468, MDA-MB-231, and MCF-7 cell line elimination in vitro

Inhibition of the development of xenograft TNBC tumors in mice

[156, 157]

Non-small-cell lung carcinoma (NSCLC)

NA

In vitro

In vivo

Selective eradication of A549, H23, and H1299 cell lines in vitro

Abrogated tumor progress of xenografts NSCLC in mice

[158]

Glioblastoma

EGFRvIII

In vitro

In vivo

Stimulation of non-significant anti-tumor response against the heterogeneous EGFRvIII expressing tumors

[159]

Mammary cancer

HER2

In vivo

PTPN2 ablation in T cells improved anti‐tumor response and CAR T‐cell efficacy in mice xenografts

[160]

Glioblastoma

EGFRvIII

In vivo

Selective elimination of EGFR-expressing tumor cells in U87 glioma cell bearing NSG mice

[161]

Melanoma

HER2

In vitro

In vivo

Elimination of SK-MEL-1 cell line in vitro

Profound or complete abrogation of tumor progress in xenograft tumors in mice

[162]

Glioblastoma

EGFRvIII

In vivo

Stimulation of antigen loss and also adaptive resistance in patients with recurrent glioblastoma upon infusion of a single dose of EGFRvIII-specific CAR T cells

[163]

Glioblastoma

HER2

In vitro

In vivo

Tandem CAR T cells affecting HER2 and IL13Rα2 attenuated tumor antigen escape in vitro and in vivo

[164]

Squamous cell carcinoma (SCC)

NA

In vitro

Selective eradication of FaDu cells in vitro

[165]

Pancreatic ductal adenocarcinoma (PDA)

HER2

In vivo

Switchable CAR-T cells trailed by injection of a Fab-based switch directed against HER2 showed higher efficacy against the advanced pancreatic tumors in NSG mice

[121]

Glioblastoma

EGFRvIII

In vivo

Intra-tumoral IL-12 delivery boosted the efficacy of CAR-T cell immunotherapy in tumor cell bearing C57Bl/6 mice

[166]

Glioblastoma

EGFRvIII

In vitro

In vivo

Notable antitumor impacts of EGFRvIII-specific CAR-T cell therapy along with PD-1 checkpoint blockade in glioblastoma cells

[167, 168]

NSCLC

NA

In vivo

Verification of the safety and feasibility of EGFR-specific CART cell against EGFR-positive NSCLC

[168]

Glioblastoma

EGFRvIII

In vivo

PD-1 ablation using CRISPR-Cas9 led to the ameliorated anti-tumor function of EGFRvIII-specific CAR T cells in tumor cell bearing mice

[169, 170]

Ovarian cancer

HER2

In vivo

Low-affinity (LA)-CARTs demonstrated lower liver injury and less systemic rates of IFN-γ than high-affinity (HA)-CARTs in xenograft mice

[171]

NSCLC

HER2

In vivo

Docetaxel (DOC) improved the infiltration of HER2-CAR T cells to tumor area in the NSCLC mice model

[172]

Various tumors

HER2

In vitro

In vivo

HA-CAR T cells produced higher rates of IFN-γ and IL-2 than LA-CAR T cells

[173]

Head and neck squamous cell carcinomas (HNSCC)

NA

In vitro

In vivo

EGFR-specific CAR T cells considerably reserved the proliferation of radio-resistant Cal33 tumor cells in vitro and mice xenografts

[174]

Glioblastoma

EGFRvIII

In vivo

EGFRvIII-specific CAR T cells reduced tumor development in mice xenografts

[175]

Various tumors

HER2

In vitro

HER2Bi-armed CART19 showed selective cytotoxicity versus various HER2+/EGFR+/CD19- breast, pancreatic, ovarian, prostate, and lung cancer cell lines

[123]

NSCLC

EGFRvIII

In vitro

In vivo

Efficient antitumor function versus A549 cell line in vitro and in vivo

[176]

Various tumors

HER2

In vivo

Restoring the antitumor impacts of HER2-specific CAR T cells by delaying epithelial-mesenchymal transition in tumor cells

[177]

Sarcoma

HER2

In vivo

Verification of the safety and efficacy of HER2-specific CAR T cells in patients with sarcoma for 6 weeks lacking apparent toxicities

[178]

Hepatocellular carcinoma (HCC)

EGFRvIII

In vitro

In vivo

EGFRvIII-specific CAR T cells established by piggyBac transposon displayed robust growth suppression versus HCC cell lines in vitro and in vivo

[179]

NSCLC

NA

In vivo

Verification of the safety and efficacy of EGFR-specific CAR T cells against EGFR-positive NSCLC patients

[180]

Ovarian cancer

HER2

In vitro

Inhibition of tumor cells proliferation by HER2-specific CAR-T cells

[181]

Colorectal cancer (CRC)

HER2

In vivo

Regression or elimination of CRC xenograft in tumor cell bearing NOD-NPG mice

[139]

Breast cancer

HER2

In vivo

A small population of HER2-specific CAR T cells could stimulate an anti-tumor response against breast cancer xenografts

[182]

Glioblastoma

EGFRvIII

In vivo

EGFRvIII-specific CAR T cells showed no clinically significant effect in patients with glioblastoma

[183]

TNBC

NA

In vitro

In vivo

Combination therapy with THZ1 and EGFR CAR T cells restored immune resistance, reduced tumor proliferation, and also metastasis in TNBC xenografts

[184]

HCC

NA

In vitro

In vivo

EGFR-specific CAR T cells demonstrated poor proliferation activity and cytotoxicity versus HCC cells

[185]

Gastric cancer

HER2

In vitro

In vivo

Robust cytotoxicity against HER2-positive gastric cancer cells

[141]

  1. PD1 programmed cell death protein 1, CRISPR clustered regularly interspaced short palindromic repeats, IFN-γ interferon gamma, NA not applicable