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HuAbDiffusion: a discrete language diffusion model used for antibody humanization.

Dongping Liu1, Xiaohu Hao1, Long Fan1,2

  • 1Production and R&D Center I of LSS (Life Science Service), GenScript Biotech Corporation, No. 28, Yongxi Rd, Nanjing, Jiangsu 211100, China.

Briefings in Bioinformatics
|December 10, 2025
PubMed
Summary
This summary is machine-generated.

HuAbDiffusion, a novel diffusion model, generates humanized antibodies from scratch, retaining or improving binding affinity. This method aids therapeutic antibody development by creating effective humanized antibodies.

Keywords:
antibodydiffusion modelgenerative modelhumanization

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Area of Science:

  • Biotechnology
  • Immunology
  • Computational Biology

Background:

  • Antibody humanization is crucial for therapeutic antibody development.
  • Existing methods for antibody humanization face limitations.

Purpose of the Study:

  • To introduce HuAbDiffusion, a discrete language diffusion model for *de novo* antibody humanization.
  • To generate whole V region sequences for humanized antibodies starting from three complementary determinant regions (CDRs).

Main Methods:

  • Utilized a discrete language diffusion model (HuAbDiffusion) for antibody humanization.
  • Generated entire V region sequences based on provided CDRs.
  • Evaluated the model on 22 monoclonal antibodies (mAbs).

Main Results:

  • HuAbDiffusion demonstrated effectiveness and superior performance compared to existing methods.
  • The model successfully retained or increased the binding affinity of humanized antibodies.
  • Pretrained language models aided in narrowing down optimal humanized antibody candidates.

Conclusions:

  • HuAbDiffusion is a promising tool for generating high-affinity humanized antibodies.
  • The model offers an efficient approach for therapeutic antibody development.
  • The developed method is accessible via the YabXnization server.