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CellOrigin advances in vivo mRNA CAR-T for HCC with Walvax partnership

China-based CellOrigin Biotech (Hangzhou) Co., Ltd. has entered a co-development agreement with Walvax Biotechnology Co., Ltd. (Shenzhen: 300142) to jointly...

CellOrigin advances in vivo mRNA CAR-T for HCC with Walvax partnership

China-based CellOrigin Biotech and Walvax Biotechnology have launched an investigator-initiated clinical program evaluating an mRNA-LNP-based in vivo GPC3-targeted CAR-T therapy for hepatocellular carcinoma, marking one of the first disclosed Chinese clinical efforts in the emerging in vivo CAR-T field.

The collaboration combines CellOrigin's cell therapy design capabilities with Walvax's GMP mRNA manufacturing infrastructure, reflecting a partnership model common among Chinese biotechnology companies. Walvax's mRNA-LNP manufacturing infrastructure originates from its COVID-19 vaccine program, and this represents the company's first disclosed co-development in therapeutic mRNA oncology.

The program's preclinical basis was presented at ASCO 2025, while CellOrigin used the ASCO 2026 meeting to simultaneously present two additional solid tumor candidates: CAR-Mix, a combination of engineered macrophages and polyclonal T cells with an IIT already underway in mesothelin-positive ovarian cancer, and TMT Engager, an LNP-mRNA-based in vivo T-cell engager designed to form tripartite conjugates between T cells, macrophages, and tumor cells.

GPC3 has become one of the leading targets in HCC cell therapy. The closest comparator is perhaps Myeloid Therapeutics, which initiated first patient dosing with MT-303 — a GPC3-targeting RNA CAR delivered via LNP — in a Phase I study for advanced HCC in July 2024, and subsequently presented first-in-human in vivo mRNA CAR data at ASCO 2025. Unlike CellOrigin's approach, Myeloid's platform programs myeloid cells rather than T cells. Carisma Therapeutics (Nasdaq: CARM), under its collaboration with Moderna, has also nominated a GPC3 in vivo CAR-macrophage development candidate for HCC, targeting macrophages rather than T cells via the same mRNA-LNP delivery framework.

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On the ex vivo side, Oricell Therapeutics reported a 66.7% objective response rate for its GPC3 CAR-T Ori-C101 in late-line HCC at ASCO 2026 and subsequently received clearance from China's National Medical Products Administration (NMPA) to advance to a Phase II trial. That provides an early efficacy benchmark against which in vivo approaches are likely to be evaluated.

Large pharma has assigned substantial premiums to in vivo mRNA-LNP CAR-T platforms at earlier stages than CellOrigin's current program. AbbVie acquired Capstan Therapeutics for up to USD 2.1 billion for a Phase I in vivo targeted LNP anti-CD19 CAR-T in autoimmune disease, and Bristol Myers Squibb acquired Orbital Therapeutics for USD 1.5 billion for a preclinical in vivo RNA-LNP CAR-T platform, also targeting CD19. Both transactions involved autoimmune indications, where early clinical signals have been cleaner and the addressable patient population broader than in solid tumor oncology. CellOrigin's IIT-first strategy — generating China domestic clinical data before seeking formal IND approval or international partnering — is consistent with an approach adopted by several Chinese cell therapy companies.


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