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

  • iScience. 2026 Feb 28;29(4):115174. doi: 10.1016/j.isci.2026.115174.
Lingli Pan  1  2 ,  Xiaomeng Zhu  3 ,  Jiaqing Zhang  4 ,  Qingyao Zhong  5 ,  Hui Wu  4 ,  Weidong Sun  6 ,  Yongming Xia  7 ,  Shibing Wang  1  8 ,  Xiangmin Tong  1  8
Affiliations
  • 1. Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
  • 2. Postgraduate Training Base Alliance of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 3. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
  • 4. Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • 5. Department of Laboratory Medicine, Hangzhou First People's Hospital, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 6. Department of Hematology, Shaoxing Central Hospital, Shaoxing, Zhejiang, China.
  • 7. Department of Hematology, Yuyao People's Hospital of Zhejiang Province, The Affiliated Yangming Hospital of Ningbo University, Yuyao, Zhejiang, China.
  • 8. Zhejiang Key Laboratory of Zero Magnetic Medicine, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
PMID: 41858619 DOI: 10.1016/j.isci.2026.115174
Abstract

Multiple myeloma (MM) is an incurable malignancy exhibiting immune evasion and resistance to Proteasome inhibitors like bortezomib. We engineered an oncolytic vaccinia virus encoding an anti-mouse CD47 nanobody (OVV-αCD47nb) that combines direct oncolysis with localized CD47-SIRPα axis blockade. OVV-αCD47nb maintained infectivity and secreted anti-CD47 nanobodies that enhanced macrophage phagocytosis of tumor cells. In murine MM models, OVV-αCD47nb suppressed tumor growth, extended survival, and induced durable responses without hematologic toxicity. Mechanistically, OVV-αCD47nb remodeled the tumor microenvironment by polarizing macrophages to M1-like phenotypes and enhancing CD8+ T cell infiltration and function. Transcriptomics revealed enriched pro-inflammatory and phagocytic pathways with downregulated Autophagy genes. OVV-αCD47nb synergized with bortezomib to overcome resistance and improve tumor control over monotherapies. This multifunctional viro-immunotherapy strategy, which integrates oncolysis, immune reprogramming, and chemosensitization, offers a promising therapeutic approach for CD47-expressing malignancies.

Keywords
cancer; immunology; medical biotechnology.
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