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Updated: Jul 7, 2025

Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
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A trispecific antibody induces potent tumor-directed T-cell activation and antitumor activity by CD3/CD28

Li Chen1, Wenjing Qian1, Fangfang Pan1

  • 1CytoCares (Shanghai) Inc., Zhangjiang Hi-Tech Park, Shanghai, 201203, China.

Immunotherapy
|December 21, 2023
PubMed

Aim: A novel CD19xCD3xCD28 trispecific antibody with a tandem single-chain variable fragments (scFv) structure was developed for the treatment of B-cell malignancies. Methods: The trispecific antibody in inducing tumor-directed T-cell activation and cytotoxicity was evaluated in vitro and in vivo and compared with its bispecific counterpart BiTE-CD19xCD3 lacking a CD28-targeting domain. Results: The trispecific antibody with a co-stimulatory domain exhibited augmented T-cell activation and memory T-cell differentiation capability and it induced faster tumor cell lysis than the bispecific antibody. RNAseq analysis revealed that the trispecific antibody modulates CD3/TCR complex-derived signal and upregulates antiapoptotic factors to influence the survival of T cells. Conclusion: By CD3/CD28 co-engagement, the trispecific antibody demonstrated its advantages in T-cell immunity and potential use as a more powerful and long-lasting T-cell engager.

Keywords:
CD28co-stimulatory receptortandem single-chain variable fragmentstrispecific T-cell engagertwo-signal model

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