Chimeric Antigen Receptor T Cells in the Treatment of Osteosarcoma (Review)

Overview

Journal Int J Oncol

Specialty Oncology

Date 2024 Feb 23

PMID 38390935

Authors

Tong Yu

Weibo Jiang

Yang Wang

Ying Zhou

Jianhang Jiao

Minfei Wu

Affiliations

Soon will be listed here.

Abstract

Osteosarcoma (OS) is a frequently occurring primary bone tumor, mostly affecting children, adolescents and young adults. Before 1970, surgical resection was the main treatment method for OS, but the clinical results were not promising. Subsequently, the advent of chemotherapy has improved the prognosis of patients with OS. However, there is still a high incidence of metastasis or recurrence, and chemotherapy has several side effects, thus making the 5‑year survival rate markedly low. Recently, chimeric antigen receptor T (CAR‑T) cell therapy represents an alternative immunotherapy approach with significant potential for hematologic malignancies. Nevertheless, the application of CAR‑T cells in the treatment of OS faces numerous challenges. The present review focused on the advances in the development of CAR‑T cells to improve their clinical efficacy, and discussed ways to overcome the difficulties faced by CAR T‑cell therapy for OS.

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References

Eriksson E, Wenthe J, Irenaeus S, Loskog A, Ullenhag G . Gemcitabine reduces MDSCs, tregs and TGFβ-1 while restoring the teff/treg ratio in patients with pancreatic cancer. J Transl Med. 2016; 14(1):282. PMC: 5041438. DOI: 10.1186/s12967-016-1037-z. View

Berdeja J, Madduri D, Usmani S, Jakubowiak A, Agha M, Cohen A . Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021; 398(10297):314-324. DOI: 10.1016/S0140-6736(21)00933-8. View

Alabanza L, Pegues M, Geldres C, Shi V, Wiltzius J, Sievers S . Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains. Mol Ther. 2017; 25(11):2452-2465. PMC: 5675490. DOI: 10.1016/j.ymthe.2017.07.013. View

Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot D, Adam J . Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med. 2014; 20(11):1301-9. DOI: 10.1038/nm.3708. View

Ajina A, Maher J . Prospects for combined use of oncolytic viruses and CAR T-cells. J Immunother Cancer. 2017; 5(1):90. PMC: 5696728. DOI: 10.1186/s40425-017-0294-6. View

Kershaw M, Wang G, Westwood J, Pachynski R, Tiffany H, Marincola F . Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2. Hum Gene Ther. 2002; 13(16):1971-80. DOI: 10.1089/10430340260355374. View

Isakoff M, Bielack S, Meltzer P, Gorlick R . Osteosarcoma: Current Treatment and a Collaborative Pathway to Success. J Clin Oncol. 2015; 33(27):3029-35. PMC: 4979196. DOI: 10.1200/JCO.2014.59.4895. View

Sugiyama D, Hinohara K, Nishikawa H . Significance of regulatory T cells in cancer immunology and immunotherapy. Exp Dermatol. 2022; 32(3):256-263. DOI: 10.1111/exd.14721. View

Dumars C, Ngyuen J, Gaultier A, Lanel R, Corradini N, Gouin F . Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma. Oncotarget. 2016; 7(48):78343-78354. PMC: 5346643. DOI: 10.18632/oncotarget.13055. View

10.

Lin Z, Wu Z, Luo W . Chimeric Antigen Receptor T-Cell Therapy: The Light of Day for Osteosarcoma. Cancers (Basel). 2021; 13(17). PMC: 8431424. DOI: 10.3390/cancers13174469. View

11.

Krenciute G, Prinzing B, Yi Z, Wu M, Liu H, Dotti G . Transgenic Expression of IL15 Improves Antiglioma Activity of IL13Rα2-CAR T Cells but Results in Antigen Loss Variants. Cancer Immunol Res. 2017; 5(7):571-581. PMC: 5746871. DOI: 10.1158/2326-6066.CIR-16-0376. View

12.

Morita R, Nishizawa S, Torigoe T, Takahashi A, Tamura Y, Tsukahara T . Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells. Cancer Sci. 2014; 105(4):389-95. PMC: 4317808. DOI: 10.1111/cas.12362. View

13.

Zeng J, Chen S, Li C, Ye Z, Lin B, Liang Y . Mesenchymal stem/stromal cells-derived IL-6 promotes nasopharyngeal carcinoma growth and resistance to cisplatin via upregulating CD73 expression. J Cancer. 2020; 11(8):2068-2079. PMC: 7052921. DOI: 10.7150/jca.37932. 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.

Wallace A, Kapoor V, Sun J, Mrass P, Weninger W, Heitjan D . Transforming growth factor-beta receptor blockade augments the effectiveness of adoptive T-cell therapy of established solid cancers. Clin Cancer Res. 2008; 14(12):3966-74. PMC: 2491721. DOI: 10.1158/1078-0432.CCR-08-0356. View

16.

DeSelm C, Palomba M, Yahalom J, Hamieh M, Eyquem J, Rajasekhar V . Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape. Mol Ther. 2018; 26(11):2542-2552. PMC: 6225039. DOI: 10.1016/j.ymthe.2018.09.008. View

17.

Wagner L, Adams V . Targeting the PD-1 pathway in pediatric solid tumors and brain tumors. Onco Targets Ther. 2017; 10:2097-2106. PMC: 5396947. DOI: 10.2147/OTT.S124008. View

18.

Geiger R, Rieckmann J, Wolf T, Basso C, Feng Y, Fuhrer T . L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. Cell. 2016; 167(3):829-842.e13. PMC: 5075284. DOI: 10.1016/j.cell.2016.09.031. View

19.

Chen J, Lopez-Moyado I, Seo H, Lio C, Hempleman L, Sekiya T . NR4A transcription factors limit CAR T cell function in solid tumours. Nature. 2019; 567(7749):530-534. PMC: 6546093. DOI: 10.1038/s41586-019-0985-x. View

20.

Santoni M, Rizzo A, Mollica V, Matrana M, Rosellini M, Faloppi L . The impact of gender on The efficacy of immune checkpoint inhibitors in cancer patients: The MOUSEION-01 study. Crit Rev Oncol Hematol. 2022; 170:103596. DOI: 10.1016/j.critrevonc.2022.103596. View