ArticleOncoimmunology2026
Targeting tumor-selective membrane-associated PCNA enables selective antibody-drug conjugate therapy.
Article in Oncoimmunology, 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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14 authors.
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Abstract
Membrane-associated proliferating cell nuclear antigen (mPCNA) is an attractive tumor-selective antigen for antibody-drug conjugate (ADC) development. We generated a chimeric IgG1 ADC, RC14-MMAE, to exploit three key properties of mPCNA that support its use as an efficient delivery platform. First, flow-cytometric and imaging analyses show abundant mPCNA surface expression on multiple tumor cell lines and in JIMT1 xenografts, providing accessible epitopes for binding. Second, comparative profiling against non-malignant counterparts and normal mouse tissues reveals minimal or undetectable mPCNA at the plasma membrane of healthy cells, indicating a sharp tumor-normal differential expected to limit off-tumor targeting and improve the therapeutic window. Third, live-cell internalization assays demonstrate that RC14 rapidly accumulates in LAMP1-positive lysosomes after engaging mPCNA, confirming efficient trafficking along the endolysosomal pathway required for protease-mediated cleavage of the valine-citrulline linker and release of monomethyl auristatin E (MMAE). Consistent with this target profile, RC14-MMAE exhibits potent antigen-dependent cytotoxicity in mPCNA-positive tumor models in NSG mice, favorable pharmacokinetics, sustained payload retention in serum, robust
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