Bispecific nanobodies targeting cxcl1 and pd-l1 and uses thereof

By constructing bispecific nanobodies targeting CXCL1 and PD-L1, the problem of low response rate of CRC patients to PD-1/PD-L1 inhibitor therapy was solved, achieving efficient blockade of CXCL1 and PD-L1, reshaping the immune microenvironment, and enhancing the therapeutic effect of CRC.

CN120795165BActive Publication Date: 2026-06-09QINGDAO UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
QINGDAO UNIV
Filing Date
2025-07-22
Publication Date
2026-06-09

AI Technical Summary

Technical Problem

Colorectal cancer (CRC) patients have a low response rate to PD-1/PD-L1 inhibitor therapy, and their immune microenvironment is highly immunosuppressed, leading to drug resistance. Traditional antibodies are insufficient in terms of penetration and immunogenicity.

Method used

We developed bispecific nanobodies targeting CXCL1 and PD-L1. By linking nanobodies that recognize the targets CXCL1 and PD-L1, we constructed nanobodies with high affinity that can simultaneously block the CXCL1 and PD-L1 signaling pathways and reshape the immune microenvironment.

Benefits of technology

It improves the effectiveness of CRC treatment, prevents drug resistance caused by immune escape, is applicable to more patients, and provides new treatment ideas.

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Abstract

This invention discloses a bispecific nanobody targeting CXCL1 and PD-L1 and its applications, belonging to the fields of antibody engineering and bioengineering technology. The bispecific nanobody targeting CXCL1 and PD-L1 comprises at least one nanobody recognizing CXCL1 and one nanobody recognizing PD-L1, with the nanobody monomers linked by a linker. The bispecific nanobody targeting PD-L1 / CXCL1 provided by this invention has a unique structure, enabling it to specifically recognize and bind to both CXCL1 and PD-L1. It achieves an affinity of 1.08 nM for CXCL1 and 1.09 nM for PD-L1, effectively preventing immune escape-induced resistance to antibody therapy, making it suitable for a wider range of patients, and providing a new approach for CRC treatment.
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Claims

1. A bispecific nanobody targeting CXCL1 and PD-L1, characterized in that, It consists of nanobodies that recognize the target CXCL1 and nanobodies that recognize the target PD-L1, with the nanobodies linked together by linkers; The amino acid sequences of the nanobodies CDR1-CDR3 that recognize the target CXCL1 are selected from any of the following combinations: Combination 1, the amino acid sequences of CDR1 to CDR3 are shown in SEQ ID NO.1 to SEQ ID NO.3, respectively; Combination 2, the amino acid sequences of CDR1 to CDR3 are shown in SEQ ID NO.4 to SEQ ID NO.6, respectively; Combination 3, the amino acid sequences of CDR1 to CDR3 are shown in SEQ ID NO.7 to SEQ ID NO.9, respectively; The amino acid sequences of the nanobodies CDR1-CDR3 that recognize the target PD-L1 are shown in SEQ ID NO.10 to SEQ ID NO.12, respectively; The amino acid sequence of the linker is shown in SEQ ID NO.

13.

2. The bispecific nanobody targeting CXCL1 and PD-L1 as described in claim 1, characterized in that, The amino acid sequence of the bispecific nanobody targeting CXCL1 and PD-L1 is shown in any one of SEQ ID NO.14 to SEQ ID NO.

21.

3. A nucleic acid molecule encoding the bispecific nanobody targeting CXCL1 and PD-L1 as described in claim 1 or 2.

4. An expression carrier, characterized in that, Includes the nucleic acid molecule as described in claim 3.

5. Transform or transfect host cells with the expression vector as described in claim 4.

6. The use of the CXCL1 and PD-L1 bispecific nanobody as described in claim 1 or 2 in the preparation of CXCL1 and PD-L1 detection reagents and / or kits.

7. CXCL1 and PD-L1 detection reagents, characterized in that, Includes the CXCL1 and PD-L1 bispecific nanobody as described in claim 1 or 2, and acceptable adjuvants and / or carriers.