ArticleFrontiers in immunology2026
A fully human afucosylated anti-GARP antibody PBA-0111 drives anti-tumor immunity through combined ADCC induction and TGF-β1 pathway blockade.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Methods: We have evaluated PBA-0111, a fully human antibody targeting Glycoprotein A Repetitions Predominant (GARP), designed to induce both antibody-dependent cellular cytotoxicity (ADCC) as well as blockage of Transforming Growth Factor Beta 1 (TGF-β1) activation. Functional assessments included Results and discussion: Our findings demonstrate that PBA-0111 exhibits ADCC activity comparable to DS-1055a-like antibody, which was not observed for ABBV-151-like antibody. PBA-0111 effectively blocks TGF-β1 activation, similar to ABBV-151-like antibody but unlike DS-1055a-like antibody. In contrast to ABBV-151, which blocks TGF-β1 activation within the pre-formed GARP/TGF-β1 complex, PBA-0111 prevents GARP/TGF-β1 complex formation itself. Importantly, PBA-0111 did not demonstrate significant binding to human platelets. In humanized mice, whether GARP was expressed on tumor cells or exclusively on Tregs, PBA-0111 treatment induced robust inhibition of tumor growth, whereas DS-1055a-like antibody did not demonstrate any statistically significant anti-tumor efficacy in these models. Tumor growth inhibition by PBA-0111 was accompanied by cytotoxic T cell activation. A similar trend of T cell activation was observed in soft tissue sarcoma patients receiving intra-tumoral injections of PBA-0111 in the Phase 0 clinical trial. Conclusion: These results underscore the therapeutic potential of PBA-0111 as a dual-functioning immunotherapy and a promising candidate for the treatment of GARP-positive cancers. This integrated mechanism may amplify anti-tumor immunity, improve synergy with checkpoint inhibitors, and provide more durable reprogramming of the tumor microenvironment than either approach alone.
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