Battling Hepatocellular Carcinoma with Bioocus GPC3 CAR-T Therapy

Patient Background

Pawan, a dedicated individual from India, was diagnosed with chronic liver disease complicated by multifocal hepatocellular carcinoma (HCC) in August 2024. At 67 years old at diagnosis (turning 68 during treatment), he faced an aggressive disease with multiple liver lesions, elevated tumor markers like AFP and PIVKA-II, anemia, liver enzyme abnormalities, and later bone metastases. Despite undergoing transarterial radioembolization (TARE), transarterial chemoembolization (TACE), immunotherapy (Atezolizumab + Bevacizumab, Tremelimumab + Durvalumab), and targeted therapies (Lenvatinib, Cabozantinib, Regorafenib), his disease progressed. Genetic testing revealed mutations in TP53, KRAS, CDKN2A, CTNNB1, and ARID1A, with low PD-L1 expression and HRD negativity, indicating limited response to certain inhibitors. Seeking advanced solutions, Pawan was referred to Tianjin Cancer Hospital through Bioocus for our autologous GPC3 CAR-T therapy under treatment number P1544.

The Treatment Journey

Pawan's CAR-T treatment began with leukapheresis on August 11, 2025, followed by manufacturing and infusion on September 2, 2025. He received a dose of 4.73 × 10^8 CAR-T cells, targeting GPC3, a marker overexpressed in HCC. Pre-infusion conditioning included fludarabine and cyclophosphamide to enhance engraftment. Post-infusion, his peripheral blood was monitored for CAR-T expansion on Days 4 (D4), 7 (D7), 10 (D10), and 12 (D12).

• D4 (September 6, 2025):CAR-T cells at 5.15% of CD3+ T cells (absolute value: 9.27 × 10^6/L), indicating initial engraftment.
• D7 (September 9, 2025):Peaked at 3.97% (6.12 × 10^7/L), showing active proliferation.
• D10 (September 12, 2025):04% (9.07 × 10^6/L).
• D12 (September 14, 2025):Stabilized at 2.82% (2.26 × 10^7/L), with total T cells at 5.4 × 10^9/L, CD3+ at 14.87%, elevated CD8+ cytotoxic T cells at 77.88%, and balanced CAR-T subsets (e.g., 2.46% CD8+CARGPC3+/CD8+).

During hospitalization from August 11 to September 15, 2025, Pawan experienced mild side effects, including low-grade fever (up to 38.5°C), fatigue, and transient liver enzyme elevations, managed supportively without severe cytokine release syndrome (CRS grade 1) or neurotoxicity. Vital signs remained stable, and supportive care included anti-infectives, nutrition, and monitoring for complications like ascites.

Outstanding Outcomes

The CAR-T expansion, though modest, demonstrated persistence and anti-tumor activity, correlating with stabilized tumor markers and no immediate progression on follow-up imaging. Pawan's case aligns with Bioocus's success in GPC3 CAR-T for HCC, where even low-level persistence can lead to durable responses in refractory patients. He was discharged in stable condition on September 15, 2025, with recommendations for ongoing monitoring, including tumor markers, liver function, and PET-CT scans. This therapy's targeted approach minimized systemic toxicity while addressing the tumor's hepatic environment.