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An oncolytic vaccinia virus encoding CD47 nanobody potentiates antitumor immunity in multiple myeloma

Lingli Pan1,2, Xiaomeng Zhu3, Jiaqing Zhang4

  • 1Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.

Iscience
|March 20, 2026
PubMed

Insights

A novel oncolytic virus engineered to target CD47 effectively treats multiple myeloma in mice. This immunotherapy enhances immune cell activity and overcomes drug resistance, offering a new strategy for difficult-to-treat cancers.

Area of Science:

  • Oncolytic virotherapy
  • Immunotherapy
  • Cancer biology

Background:

  • Multiple myeloma (MM) is an incurable cancer characterized by immune evasion and resistance to therapies like bortezomib.
  • The CD47-SIRPα axis is a key immune checkpoint that promotes tumor cell survival by inhibiting phagocytosis.
  • Developing novel therapeutic strategies is crucial for overcoming MM resistance and improving patient outcomes.

Purpose of the Study:

  • To engineer a multifunctional oncolytic vaccinia virus (OVV) encoding an anti-mouse CD47 nanobody (OVV-αCD47nb).
  • To evaluate the efficacy of OVV-αCD47nb in preclinical multiple myeloma models.
  • To investigate the mechanisms underlying OVV-αCD47nb's therapeutic effects and its synergy with bortezomib.

Main Methods:

  • Engineering of an oncolytic vaccinia virus to express an anti-CD47 nanobody.
  • Administration of OVV-αCD47nb to murine models of multiple myeloma.
  • Assessment of tumor growth, survival, immune cell infiltration, and gene expression.
  • Combination therapy studies with bortezomib.

Main Results:

  • OVV-αCD47nb demonstrated infectivity and secreted functional nanobodies that enhanced macrophage phagocytosis.
  • Treatment with OVV-αCD47nb suppressed tumor growth, extended survival, and induced durable responses in MM models without significant toxicity.
  • OVV-αCD47nb reprogrammed the tumor microenvironment, promoting M1-like macrophages and enhancing CD8+ T cell activity.
  • Transcriptomic analysis revealed increased pro-inflammatory and phagocytic pathways and decreased autophagy.
  • OVV-αCD47nb synergized with bortezomib to overcome drug resistance and improve anti-tumor efficacy.

Conclusions:

  • OVV-αCD47nb is a promising multifunctional viro-immunotherapy for CD47-expressing malignancies like multiple myeloma.
  • This strategy combines oncolysis, immune reprogramming, and chemosensitization to overcome therapeutic resistance.
  • Further investigation is warranted to explore its clinical potential in treating hematologic malignancies.
Keywords:
cancerimmunologymedical biotechnology

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