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晚期胃癌免疫治疗的现状
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Abstract:
作为最常见的实体瘤之一,胃癌已被证明是全球第三大死因。胃癌的症状通常不明显,因此很难在早期发现。因此,胃癌一旦在患者中被发现,就已经处于晚期,由于治疗无效和多重耐药,预后较差。最近在了解癌症微环境方面的进展显著促进了晚期胃癌免疫疗法的发展。免疫疗法可以诱导胃癌患者的免疫反应,从而导致癌细胞的破坏。与传统疗法相比,免疫疗法已显示出强大的疗效和可耐受的毒性。因此,这种治疗晚期胃癌的新策略越来越受欢迎。本文综述了免疫治疗晚期胃癌的最新进展,如免疫检查点抑制剂、过继细胞疗法、VEGF抑制剂、癌症疫苗和CAR-T细胞疗法等。
As one of the most common solid tumors, gastric cancer has been proven to be the third leading cause of death worldwide. The symptoms of gastric cancer are usually not obvious, so it is difficult to detect them early. Therefore, once gastric cancer is detected in patients, it is already in the advanced stage, and due to ineffective treatment and multiple drug resistance, the prognosis is poor. The recent progress in understanding the cancer microenvironment has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce an immune response in gastric cancer patients, leading to the destruction of cancer cells. Compared with traditional therapies, immunotherapy has shown strong efficacy and tolerable toxicity. Therefore, this new strategy for treating advanced gastric cancer is becoming increasingly popular. This article reviews the latest advances in immunotherapy for advanced gastric cancer, such as immune checkpoint inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines, and CAR-T cell therapy.
[1] | Ferlay, J., Colombet, M., Soerjomataram, I., et al. (2019) Estimating the Global Cancer Incidence and Mortality in 2018: GLOBOCAN Sources and Methods. International Journal of Cancer, 144, 1941-1953. https://doi.org/10.1002/ijc.31937 |
[2] | H?gner, A. and Moehler, M. (2022) Immunotherapy in Gastric Cancer. Current Oncology (Toronto, Ont.), 29, 1559-1574. https://doi.org/10.3390/curroncol29030131 |
[3] | Jin, X., Liu, Z., Yang, D., et al. (2022) Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Frontiers in Immunology, 13, Article ID: 948647. https://doi.org/10.3389/fimmu.2022.948647 |
[4] | Koizumi, W., et al. (2008) S-1 plus Cisplatin versus S-1 Alone for First-Line Treatment of Advanced Gastric Cancer (SPIRITS Trial): A Phase III Trial. The Lancet Oncology, 9, 215-221. https://doi.org/10.1016/S1470-2045(08)70035-4 |
[5] | Kawazoe, A., Fukuoka, S., Nakamura, Y., et al. (2020) Lenvatinib plus Pembrolizumab in Patients with Advanced Gastric Cancer in the First-Line or Second-Line Setting (EPOC1706): An Open-Label, Single-Arm, Phase 2 Trial. The Lancet Oncology, 21, 1057-1065. https://doi.org/10.1016/S1470-2045(20)30271-0 |
[6] | Xie, J., Fu, L. and Jin, L. (2021) Immunotherapy of Gastric Cancer: Past, Future Perspective and Challenges. Pathology, Research and Practice, 218, Article ID: 153322. https://doi.org/10.1016/j.prp.2020.153322 |
[7] | Postow, M.A., Callahan, M.K. and Wolchok, J.D. (2015) Immune Checkpoint Blockade in Cancer Therapy. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 33, 1974-1982. https://doi.org/10.1200/JCO.2014.59.4358 |
[8] | Kawazoe, A., Shitara, K., Boku, N., et al. (2021) Current Status of Immunotherapy for Advanced Gastric Cancer. Japanese Journal of Clinical Oncology, 51, 20-27. https://doi.org/10.1093/jjco/hyaa202 |
[9] | Robert, C., Thomas, L., Bondarenko, I., et al. (2011) Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma. The New England Journal of Medicine, 364, 2517-2526. https://doi.org/10.1056/NEJMoa1104621 |
[10] | Kato, K., et al. (2019) A Subanalysis of Japanese Patients in a Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nivolumab for Patients with Advanced Gastric or Gastro-Esophageal Junction Cancer Refractory to, or Intolerant of, at Least Two Previous Chemotherapy Regimens (ONO-4538-12, ATTRACTION-2). Gastric Cancer: Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 22, 344-354. |
[11] | Doi, T., et al. (2019) Phase 1 Trial of Avelumab (Anti-PD-L1) in Japanese Patients with Advanced Solid Tumors, Including Dose Expansion in Patients with Gastric or Gastroesophageal Junction Cancer: The JAVELIN Solid Tumor JPN Trial. Gastric Cancer: Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 22, 817-827. https://doi.org/10.1007/s10120-018-0903-1 |
[12] | Fuchs, C.S., Doi, T., Jang, R.W., et al. (2018) Safety and Efficacy of Pembrolizumab Monotherapy in Patients with Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncology, 4, E180013. https://doi.org/10.1001/jamaoncol.2018.0013 |
[13] | Shitara, K., et al. (2020) Efficacy and Safety of Pembrolizumab or Pembrolizumab plus Chemotherapy vs Chemotherapy Alone for Patients with First-Line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncology, 6, 1-10. |
[14] | Doroshow, D.B., Bhalla, S., Beasley, M.B., et al. (2021) PD-L1 as a Biomarker of Response to Immune-Checkpoint Inhibitors. Nature Reviews. Clinical Oncology, 18, 345-362. https://doi.org/10.1038/s41571-021-00473-5 |
[15] | Bang, Y.J., Ruiz, E.Y., Van Cutsem, E., et al. (2018) Phase III, Randomised Trial of Avelumab versus Physician’s Choice of Chemotherapy as Third-Line Treatment of Patients with Advanced Gastric or Gastro-Oesophageal Junction Cancer: Primary Analysis of JAVELIN Gastric 300. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 29, 2052-2060. https://doi.org/10.1093/annonc/mdy264 |
[16] | Bang, Y.J., Cho, J.Y., Kim, Y.H., et al. (2017) Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 23, 5671-5678. https://doi.org/10.1158/1078-0432.CCR-17-0025 |
[17] | Kelly, R.J., Lee, J., Bang, Y.J., et al. (2020) Safety and Efficacy of Durvalumab and Tremelimumab Alone or in Combination in Patients with Advanced Gastric and Gastroesophageal Junction Adenocarcinoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 26, 846-854. https://doi.org/10.1158/1078-0432.CCR-19-2443 |
[18] | Pang, X., et al. (2023) Cadonilimab, a Tetravalent PD-1/CTLA-4 Bispecific Antibody with Trans-Binding and Enhanced Target Binding Avidity. MAbs, 15, Article ID: 2180794. https://doi.org/10.1080/19420862.2023.2180794 |
[19] | Zhang, L., Wang, Y., Li, Z., et al. (2021) Clinicopathological Features of Tumor Mutation Burden, Epstein-Barr Virus Infection, Microsatellite Instability and PD-L1 Status in Chinese Patients with Gastric Cancer. Diagnostic Pathology, 16, Article No. 38. https://doi.org/10.1186/s13000-021-01099-y |
[20] | Gao, X., Mi, Y., Guo, N., et al. (2017) Cytokine-Induced Killer Cells as Pharmacological Tools for Cancer Immunotherapy. Frontiers in Immunology, 8, Article No. 774. https://doi.org/10.3389/fimmu.2017.00774 |
[21] | Moreno, V., Hernandez, T., De Miguel, M., et al. (2021) Adoptive Cell Therapy for Solid Tumors: Chimeric Antigen Receptor T Cells and Beyond. Current Opinion in Pharmacology, 59, 70-84. https://doi.org/10.1016/j.coph.2021.05.004 |
[22] | Shen, X., et al. (2007) Persistence of Tumor Infiltrating Lymphocytes in Adoptive Immunotherapy Correlates with Telomere Length. Journal of Immunotherapy (Hagerstown, Md.: 1997), 30, 123-129. https://doi.org/10.1097/01.cji.0000211321.07654.b8 |
[23] | Cao, B., Liu, M., Huang, J., et al. (2021) Development of Mesothelin-Specific CAR NK-92 Cells for the Treatment of Gastric Cancer. International Journal of Biological Sciences, 17, 3850-3861. https://doi.org/10.7150/ijbs.64630 |
[24] | Ishikawa, T., Okayama, T., Sakamoto, N., et al. (2018) Phase I Clinical Trial of Adoptive Transfer of Expanded Natural Killer Cells in Combination with IgG1 Antibody in Patients with Gastric or Colorectal Cancer. International Journal of Cancer, 142, 2599-2609. https://doi.org/10.1002/ijc.31285 |
[25] | Gabrilovich, D.I., Chen, H.L., Girgis, K.R., et al. (1996) Production of Vascular Endothelial Growth Factor by Human Tumors Inhibits the Functional Maturation of Dendritic Cells. Nature Medicine, 2, 1096-1103. https://doi.org/10.1038/nm1096-1096 |
[26] | Herbst, R.S., Arkenau, H.T., Santana-Davila, R., et al. (2019) Ramucirumab plus Pembrolizumab in Patients with Previously Treated Advanced Non-Small-Cell Lung Cancer, Gastro-Oesophageal Cancer, or Urothelial Carcinomas (JVDF): A Multicohort, Non-Randomised, Open-Label, Phase 1a/B Trial. The Lancet Oncology, 20, 1109-1123. https://doi.org/10.1016/S1470-2045(19)30458-9 |
[27] | Pardi, N., Hogan, M.J. and Weissman, D. (2020) Recent Advances in MRNA Vaccine Technology. Current Opinion in Immunology, 65, 14-20. https://doi.org/10.1016/j.coi.2020.01.008 |
[28] | Ajani, J.A., et al. (2006) An Open-Label, Multinational, Multicenter Study of G17DT Vaccination Combined with Cisplatin and 5-Fluorouracil in Patients with Untreated, Advanced Gastric or Gastroesophageal Cancer: The GC4 Study. Cancer, 106, 1908-1916. https://doi.org/10.1002/cncr.21814 |
[29] | Sato, Y., Shomura, H., Maeda, Y., et al. (2003) Immunological Evaluation of Peptide Vaccination for Patients with Gastric Cancer Based on Pre-Existing Cellular Response to Peptide. Cancer Science, 94, 802-808. https://doi.org/10.1111/j.1349-7006.2003.tb01522.x |
[30] | Lv, J., Zhao, R., Wu, D., et al. (2019) Mesothelin Is a Target of Chimeric Antigen Receptor T Cells for Treating Gastric Cancer. Journal of Hematology & Oncology, 12, Article No. 18. https://doi.org/10.1186/s13045-019-0704-y |
[31] | Caruso, H.G., Heimberger, A.B. and Cooper, L.J.N. (2019) Steering CAR T Cells to Distinguish Friend from Foe. Oncoimmunology, 8, E1271857. https://doi.org/10.1080/2162402X.2016.1271857 |
[32] | B?bnowska, D., Grywalska, E., Nied?wiedzka-Rystwej, P., et al. (2020) CAR-T Cell Therapy—An Overview of Targets in Gastric Cancer. Journal of Clinical Medicine, 9, Article No. 1894. https://doi.org/10.3390/jcm9061894 |