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Background <p>Acute myeloid leukemia (AML) still lacks an ideal immunotherapy target. CD38 serves as a potential therapeutic target for AML. Classical bispecific antibody (BsAb) requires continuous infusion due to small molecular size and short half-life.</p> Methods <p>The anti-human CD38 single-chain variable fragment (scFv) and anti-human CD3 scFv were cloned to expression plasmids. ExpiCHO-S cells were transfected, and the anti-CD38/anti-CD3 bispecific antibody (38-3-BsAbs) in CHO supernatants was efficiently purified. The anti-AML efficacy of 38-3-BsAbs was evaluated in vitro and in vivo.</p> Results <p>The novel loop structures of non-human IgG Fc fused and human IgG1 Fc fused anti-CD38/anti-CD3 BsAbs, 38-3-loop-BsAb and 38-3-loopFc-BsAb, were designed and produced. Both 38-3-loop-BsAb and 38-3-loopFc-BsAb showed excellent anti-AML effects at low concentrations in vitro. AML xenograft NOD-scid IL2gamma<sup>null</sup> (NSG) mouse model was adopted to evaluate therapeutic effects of 38-3-BsAb. The anti-leukemic effect of 38-3-loopFc-BsAb was superior.</p> Conclusions <p>We report on new structures of 38-3 bispecific antibody and demonstrate their anti-tumor effect in the treatment of AML.</p>

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Novel loop structure of human IgG1 Fc fused CD38 targeted bispecific antibodies and their anti-tumor effect in acute myeloid leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月28日

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  • Shisen Wang,
  • Manling Chen,
  • Tong Zhou,
  • Chengcai Guo,
  • Zhifeng Yan,
  • Yingxi Xu,
  • Haiyan Xing,
  • Kejing Tang,
  • Zheng Tian,
  • Qing Rao,
  • Shaowei Qiu,
  • Ying Wang,
  • Runxia Gu,
  • Min Wang,
  • Jianxiang Wang

摘要

Background

Acute myeloid leukemia (AML) still lacks an ideal immunotherapy target. CD38 serves as a potential therapeutic target for AML. Classical bispecific antibody (BsAb) requires continuous infusion due to small molecular size and short half-life.

Methods

The anti-human CD38 single-chain variable fragment (scFv) and anti-human CD3 scFv were cloned to expression plasmids. ExpiCHO-S cells were transfected, and the anti-CD38/anti-CD3 bispecific antibody (38-3-BsAbs) in CHO supernatants was efficiently purified. The anti-AML efficacy of 38-3-BsAbs was evaluated in vitro and in vivo.

Results

The novel loop structures of non-human IgG Fc fused and human IgG1 Fc fused anti-CD38/anti-CD3 BsAbs, 38-3-loop-BsAb and 38-3-loopFc-BsAb, were designed and produced. Both 38-3-loop-BsAb and 38-3-loopFc-BsAb showed excellent anti-AML effects at low concentrations in vitro. AML xenograft NOD-scid IL2gammanull (NSG) mouse model was adopted to evaluate therapeutic effects of 38-3-BsAb. The anti-leukemic effect of 38-3-loopFc-BsAb was superior.

Conclusions

We report on new structures of 38-3 bispecific antibody and demonstrate their anti-tumor effect in the treatment of AML.