Glypican-3-Targeted CAR T Cell Therapy in An Advanced Hepatocellular Carcinoma Patient: A Case Report

Purpose: Glypican-3 (GPC3) is highly expressed in most hepatocellular carcinomas (HCCs) and represents a promising cancer target.Most previous clinical trials of GPC3-targeted chimeric antigen receptor (CAR) T cells have demonstrated preliminary safety but unsatisfactory tumor response.However, reports on the detailed toxicity and efficacy profile of GPC3 CAR T cells in HCC patients are limited.We aim to report preliminary results of our GPC3 CAR T cells.Methods and results: A 66-yearold patient with a history of recurrent HCC had undergone multiple treatments.Immunohistochemistry revealed high GPC3 expression in his tumour tissue.After enrollment in our single-arm, open-label phase I trial (NCT05123209), the patient received fludarabine and cyclophosphamide lymphodepletion before a single infusion of GPC3-targeted CAR T cells.The treatment was well tolerated.Only grade 1 cytokine release syndrome (CRS) was observed on Day 4 post-infusion, manifested by low-grade fever and elevations in IL-6 and IL-10.Symptoms were resolved rapidly with tocilizumab and dexamethasone.No severe adverse events were noted.CAR T cells proliferated and peaked at Day 7 in the peripheral blood.A transient reduction of alpha-fetoprotein (AFP) was observed on Day 21.However, computed tomography on Day 28 demonstrated an enlargement of the primary lesion, accompanied by a rise in AFP, indicating progressive disease (PD).Conclusions of the study: This case illustrates that GPC3directed CAR T cell therapy was safe and feasible for an advanced HCC patient, but did not achieve objective remission within four weeks.Further optimization of treatment strategies was warranted for improved response.