Use of competitive polypeptide against ythdf1 in combination with pd-l1 antibody in preparation of drugs for treating tumors

By designing competitive peptides to target the YTHDF1-ARID1A protein interface and combining them with PD-L1 antibodies, the innate immune signaling pathway was activated, solving the problem of limited clinical success of existing drugs targeting the innate immune pathway. This resulted in enhanced CD8+ T cell infiltration and tumor growth inhibition in a mouse tumor model.

CN122229983APending Publication Date: 2026-06-19ZHONGDA HOSPITAL SOUTHEAST UNIV
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Patent Information

Application Number
CN202610398941.8
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-03-30
Publication Date
2026-06-19

AI Technical Summary

Technical Problem

Existing drugs targeting innate immune pathways have limited clinical success, and research on tumor-related drugs targeting YTHDF1 has not yet entered clinical application, lacking research on its non-m6A modification function.

Method used

A competitive peptide was designed to target the interaction interface between YTHDF1 and ARID1A proteins and combined with a PD-L1 antibody to activate the innate immune signaling pathway. By inhibiting the direct protein-protein interaction between YTHDF1 and ARID1A through the competitive peptide, the cGAS-STING-IRF3 innate immune signaling pathway was activated.

Benefits of technology

In a mouse tumor model, it enhanced CD8+ T cell infiltration, improved the sensitivity of immune checkpoint blockade, improved the tumor immune microenvironment, increased the killing ability of CD8+ T cells, and significantly inhibited tumor growth.

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Abstract

This invention discloses the application of a competitive peptide targeting YTHDF1 in combination with a PD-L1 antibody in the preparation of drugs for treating tumors, belonging to the field of biomedical technology. Specifically, this invention relates to the application of a competitive peptide targeting the interaction interface between YTHDF1 and ARID1A proteins in the preparation of drugs for treating tumors; wherein, the targeting sequence of the competitive peptide corresponds to the interface between amino acid segments 495-559 of the YTHDF1 protein and amino acid segments 1611-2285 of the ARID1A protein, and includes a functional fragment of the YTHDF1 protein nuclear localization signal sequence. Compared with the prior art, this invention reveals for the first time that the mRNA-binding protein YTHDF1 has a previously undiscovered nuclear function, which can inhibit the activation of innate immune responses independently of m⁶A recognition. YTHDF1 and the chromatin remodeling factor ARID1A act synergistically in their interactions with immune-related genomic regions. In a mouse tumor model, the competitive peptide enhances CD8+. + T cell infiltration and increased sensitivity to immune checkpoint blockade, combined with PD-L1 antibody blockade therapy, can significantly improve the tumor immune microenvironment and increase CD8+. + T cells kill tumors and inhibit their growth.
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Citation Information

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