ArticleAntibody therapeutics2026
Conformational epitope engagement by anti-MSLN ADC RC88 confers resistance to soluble mesothelin.
Article in Antibody therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Mesothelin (MSLN) is a therapeutic target for antibody-drug conjugates (ADCs) due to its tumor-selective overexpression. However, soluble MSLN (sMSLN) in circulation compromises efficacy by acting as a decoy. RC88 is a clinical-stage ADC composed of a humanized anti-MSLN antibody conjugated to a monomethyl auristatin E (MMAE) payload. This study elucidates the unique binding mechanism that allows RC88 to maintain superior efficacy despite sMSLN interference. Methods: We characterized the RC88-MSLN interaction via structural analysis and mutagenesis. The impact of sMSLN on binding was assessed using competitive cellular assays. In vitro internalization kinetics and cytotoxicity were evaluated to determine the therapeutic potential. Results: RC88 targets a high-affinity N-terminal epitope overlapping the MUC16/CA125-binding site, competitively inhibiting this interaction. Notably, due to the structural flexibility of MSLN, RC88 also engages a secondary, low affinity juxtamembrane epitope at the C-terminus. This conformational binding confers resistance to sMSLN interference and enhanced tumor cell retention. Conclusion: Our findings demonstrate that RC88 utilizes a novel conformational binding strategy to overcome the limitations of soluble antigen interference. These findings provide a mechanistic rationale for the encouraging clinical activity of RC88 and suggest that conformational epitope targeting represents a promising strategy for overcoming sMSLN interference in MSLN-positive cancers.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.