From Anti-HER-2 to Anti-HER-2-CAR-T Cells: An Evolutionary Immunotherapy Approach for Gastric Cancer

Overview

Journal J Inflamm Res

Publisher Dove Medical Press

Date 2022 Jul 25

PMID 35873388

Authors

Jiangang Sun

Xiaojing Li

Peng Chen

Yongshun Gao

Affiliations

Soon will be listed here.

Abstract

Current Therapeutic modalities provide no survival advantage to gastric cancer (GC) patients. Targeting the human epidermal growth factor receptor-2 (HER-2) is a viable therapeutic strategy against advanced HER-2 positive GC. Antibody-drug conjugates, small-molecule tyrosine kinase inhibitors (TKIs), and bispecific antibodies are emerging as novel drug forms that may abrogate the resistance to HER-2-specific drugs and monoclonal antibodies. Chimeric antigen receptor-modified T cells (CAR-T) targeting HER-2 have shown considerable therapeutic potential in GC and other solid tumors. However, due to the high heterogeneity along with the complex tumor microenvironment (TME) of GC that often leads to immune escape, the immunological treatment of GC still faces many challenges. Here, we reviewed and discussed the current progress in the research of anti-HER-2-CAR-T cell immunotherapy against GC.

Citing Articles

Evolving Landscape of HER2-Targeted Therapies for Gastric Cancer Patients.

He L, Liu B, Wang Z, Han Q, Chen H Curr Treat Options Oncol. 2025; .

PMID: 40056280 DOI: 10.1007/s11864-025-01300-0.

Efficacy and safety of different drugs in patients with HER2-positive gastric cancer: network meta-analysis.

Zhang J, Yuan C, Ma X Syst Rev. 2025; 14(1):40.

PMID: 39930467 PMC: 11808970. DOI: 10.1186/s13643-025-02777-4.

HER2 in Gastric Cancer: A Comprehensive Analysis Combining Meta-Analysis and DCE-MRI Radiomics.

Shen L, Li Y, Huang H, Lu Z, Chen B Cancer Control. 2024; 31:10732748241293699.

PMID: 39448273 PMC: 11528791. DOI: 10.1177/10732748241293699.

Novel immunotherapeutic approaches in gastric cancer.

Yang M, Lin W, Huang J, Mannucci A, Luo H Precis Clin Med. 2024; 7(4):pbae020.

PMID: 39397869 PMC: 11467695. DOI: 10.1093/pcmedi/pbae020.

Clinicopathological characteristics and prognosis of combined hepatocellular cholangiocarcinoma.

Li Y, He D, Lu Z, Gu X, Liu X, Chen M BMC Cancer. 2024; 24(1):1232.

PMID: 39375615 PMC: 11457400. DOI: 10.1186/s12885-024-12970-8.

References

Bang Y, Van Cutsem E, Feyereislova A, Chung H, Shen L, Sawaki A . Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376(9742):687-97. DOI: 10.1016/S0140-6736(10)61121-X. View

Mohammadi M, Jeddi-Tehrani M, Golsaz-Shirazi F, Arjmand M, Bahadori T, Judaki M . A Novel Anti-HER2 Bispecific Antibody With Potent Tumor Inhibitory Effects and . Front Immunol. 2021; 11:600883. PMC: 7927792. DOI: 10.3389/fimmu.2020.600883. View

Hecht J, Bang Y, Qin S, Chung H, Xu J, Park J . Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial. J Clin Oncol. 2015; 34(5):443-51. DOI: 10.1200/JCO.2015.62.6598. View

Saeki N, Gu J, Yoshida T, Wu X . Prostate stem cell antigen: a Jekyll and Hyde molecule?. Clin Cancer Res. 2010; 16(14):3533-8. PMC: 2905486. DOI: 10.1158/1078-0432.CCR-09-3169. View

Quijano-Rubio A, Yeh H, Park J, Lee H, Langan R, Boyken S . De novo design of modular and tunable protein biosensors. Nature. 2021; 591(7850):482-487. PMC: 8074680. DOI: 10.1038/s41586-021-03258-z. View

Thuss-Patience P, Shah M, Ohtsu A, Van Cutsem E, Ajani J, Castro H . Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017; 18(5):640-653. DOI: 10.1016/S1470-2045(17)30111-0. View

Modi S, Saura C, Yamashita T, Park Y, Kim S, Tamura K . Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2019; 382(7):610-621. PMC: 7458671. DOI: 10.1056/NEJMoa1914510. View

Skidmore L, Sakamuri S, Knudsen N, Hewet A, Milutinovic S, Barkho W . ARX788, a Site-specific Anti-HER2 Antibody-Drug Conjugate, Demonstrates Potent and Selective Activity in HER2-low and T-DM1-resistant Breast and Gastric Cancers. Mol Cancer Ther. 2020; 19(9):1833-1843. DOI: 10.1158/1535-7163.MCT-19-1004. View

Barok M, Le Joncour V, Martins A, Isola J, Salmikangas M, Laakkonen P . ARX788, a novel anti-HER2 antibody-drug conjugate, shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer. Cancer Lett. 2020; 473:156-163. DOI: 10.1016/j.canlet.2019.12.037. View

10.

Vora P, Venugopal C, Salim S, Tatari N, Bakhshinyan D, Singh M . The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma. Cell Stem Cell. 2020; 26(6):832-844.e6. DOI: 10.1016/j.stem.2020.04.008. View

11.

Bueno C, Velasco-Hernandez T, Gutierrez-Aguera F, Zanetti S, Baroni M, Sanchez-Martinez D . CD133-directed CAR T-cells for MLL leukemia: on-target, off-tumor myeloablative toxicity. Leukemia. 2019; 33(8):2090-2125. PMC: 6756031. DOI: 10.1038/s41375-019-0418-8. View

12.

Pang N, Shi J, Qin L, Chen A, Tang Y, Yang H . IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. J Hematol Oncol. 2021; 14(1):118. PMC: 8323212. DOI: 10.1186/s13045-021-01128-9. View

13.

Yu J, Huang C, Sun Y, Su X, Cao H, Hu J . Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial. JAMA. 2019; 321(20):1983-1992. PMC: 6547120. DOI: 10.1001/jama.2019.5359. View

14.

Tao K, He M, Tao F, Xu G, Ye M, Zheng Y . Development of NKG2D-based chimeric antigen receptor-T cells for gastric cancer treatment. Cancer Chemother Pharmacol. 2018; 82(5):815-827. DOI: 10.1007/s00280-018-3670-0. View

15.

Yu S, Liu Q, Han X, Qin S, Zhao W, Li A . Development and clinical application of anti-HER2 monoclonal and bispecific antibodies for cancer treatment. Exp Hematol Oncol. 2017; 6:31. PMC: 5704598. DOI: 10.1186/s40164-017-0091-4. View

16.

Zhang E, Yang P, Gu J, Wu H, Chi X, Liu C . Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancreatic malignancy. J Hematol Oncol. 2018; 11(1):102. PMC: 6090669. DOI: 10.1186/s13045-018-0646-9. View

17.

Brown M, Ebert L, Gargett T . Clinical chimeric antigen receptor-T cell therapy: a new and promising treatment modality for glioblastoma. Clin Transl Immunology. 2019; 8(5):e1050. PMC: 6526894. DOI: 10.1002/cti2.1050. View

18.

Nellan A, Rota C, Majzner R, Lester-McCully C, Griesinger A, Mulcahy Levy J . Durable regression of Medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. J Immunother Cancer. 2018; 6(1):30. PMC: 5925833. DOI: 10.1186/s40425-018-0340-z. View

19.

Zhang C, Wang Z, Yang Z, Wang M, Li S, Li Y . Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA Metastatic Colorectal Cancers. Mol Ther. 2017; 25(5):1248-1258. PMC: 5417843. DOI: 10.1016/j.ymthe.2017.03.010. View

20.

Gradishar W . Emerging approaches for treating HER2-positive metastatic breast cancer beyond trastuzumab. Ann Oncol. 2013; 24(10):2492-2500. DOI: 10.1093/annonc/mdt217. View