Albelda, S. M. CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn. Nat. Rev. Clin. Oncol. 21, 47–66 (2024).
Fu, Q. et al. RUNX-3-expressing CAR T cells targeting glypican-3 in patients with heavily pretreated advanced hepatocellular carcinoma: a phase I trial. EClinicalMedicine 63, 102175 (2023).
Shi, D. et al. Chimeric antigen receptor-glypican-3 T-cell therapy for advanced hepatocellular carcinoma: results of phase I trials. Clin. Cancer Res. 26, 3979–3989 (2020).
Du, G. et al. Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy. Front. Immunol. 15, 1431211 (2024).
Giardino Torchia, M. L. et al. Rational design of chimeric antigen receptor T cells against glypican 3 decouples toxicity from therapeutic efficacy. Cytotherapy 24, 720–732 (2022).
Yang, J. D. et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat. Rev. Gastroenterol. Hepatol. 16, 589–604 (2019).
Finn, R. S. et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 382, 1894–1905 (2020).
Abou-Alfa, G. K. et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 1, EVIDoa2100070 (2022).
Rizzo, A. & Brandi, G. Biochemical predictors of response to immune checkpoint inhibitors in unresectable hepatocellular carcinoma. Cancer Treat. Res. Commun. 27, 100328 (2021).
Wang, Y. et al. Atezolizumab plus bevacizumab combination enables an unresectable hepatocellular carcinoma resectable and links immune exclusion and tumor dedifferentiation to acquired resistance. Exp. Hematol. Oncol. 10, 45 (2021).
Fowler, N. H. et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat. Med. 28, 325–332 (2022).
Schuster, S. J. et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N. Engl. J. Med. 380, 45–56 (2019).
Shin, M. H. et al. Recent advances in CAR-based solid tumor immunotherapy. Cells 12, 1606 (2023).
Steffin, D. et al. Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers. Nature 637, 940–946 (2025).
Qi, C. et al. Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician’s choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial. Lancet 405, 2049–2060 (2025).
Ning, S. et al. Glypican-3, a novel prognostic marker of hepatocellular cancer, is related with postoperative metastasis and recurrence in hepatocellular cancer patients. Mol. Biol. Rep. 39, 351–357 (2012).
Guo, M., Zhang, H., Zheng, J. & Liu, Y. Glypican-3: a new target for diagnosis and treatment of hepatocellular carcinoma. J. Cancer 11, 2008–2021 (2020).
Giardino Torchia, M. L. & Moody, G. DIALing-up the preclinical characterization of gene-modified adoptive cellular immunotherapies. Front. Immunol. 14, 1264882 (2023).
Tauriello, D. V. F., Sancho, E. & Batlle, E. Overcoming TGFβ-mediated immune evasion in cancer. Nat. Rev. Cancer 22, 25–44 (2022).
An, Y. et al. Transforming growth factor-β and peripheral regulatory cells are negatively correlated with the overall survival of hepatocellular carcinoma. World J. Gastroenterol. 24, 2733–2740 (2018).
Shirai, Y. et al. Plasma transforming growth factor-β 1 in patients with hepatocellular carcinoma. Comparison with chronic liver diseases. Cancer 73, 2275–2279 (1994).
Narayan, V. et al. PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial. Nat. Med. 28, 724–734 (2022).
Park, B. V. et al. TGFβ1-mediated SMAD3 enhances PD-1 expression on antigen-specific T cells in cancer. Cancer Discov. 6, 1366–1381 (2016).
Abou-Alfa, G. K. et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N. Engl. J. Med. 379, 54–63 (2018).
Bruix, J. et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 389, 56–66 (2017).
Zhu, A. X. et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 20, 282–296 (2019).
Kudo, M. et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391, 1163–1173 (2018).
Llovet, J. M. et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378–390 (2008).
Sun, L. et al. Shed antigen-induced blocking effect on CAR-T cells targeting glypican-3 in hepatocellular carcinoma. J. Immunother. Cancer. 9, e001875 (2021).
Ren, Z. et al. Sintilimab plus bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomized, open-label, phase 2-3 study. Lancet 22, 977–990 (2021).
