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Immunological conversion of solid tumours using a bispecific nanobioconjugate for cancer immunotherapy

Nature Nanotechnology volume 17, pages 1332–1341 (2022)Cite this article

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Abstract

Solid tumours display a limited response to immunotherapies. By contrast, haematological malignancies exhibit significantly higher response rates to immunotherapies as compared with solid tumours. Among several microenvironmental and biological disparities, the differential expression of unique immune regulatory molecules contributes significantly to the interaction of blood cancer cells with immune cells. The self-ligand receptor of the signalling lymphocytic activation molecule family member 7 (SLAMF7), a molecule that is critical in promoting the body’s innate immune cells to detect and engulf cancer cells, is expressed nearly exclusively on the cell surface of haematologic tumours, but not on solid ones. Here we show that a bispecific nanobioconjugate that enables the decoration of SLAMF7 on the surface of solid tumours induces robust phagocytosis and activates the phagocyte cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS–STING) pathway, sensitizing the tumours to immune checkpoint blockade. Our findings support an immunological conversion strategy that uses nano-adjuvants to improve the effectiveness of immunotherapies for solid tumours.

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Fig. 1: The BiTNHER nanoparticle targets and converts specific non-haematopoietic cancer cells into haematopoietic-like cancer cells.
Fig. 2: The combination of anti-CD47 and BiTNHER induces targeted phagocytosis of cancer cells and subsequent macrophage activation.
Fig. 3: Combined treatment with BiTNHER and anti-CD47 induces anti-tumour immune responses in the HER2/neu-expressing mouse tumour model.
Fig. 4: STING activation is involved in the immune response mediated by triple combination treatment.
Fig. 5: Combination treatment with BiTNFo, anti-CD47 and anti-PD1 generated in situ tumour vaccine effects and induced systemic anti-tumour effects against 4T1 tumour metastasis.

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Data availability

The data supporting the findings of this study are available within the article and its Supplementary Information. The datasets generated and analysed during the study are publicly available at https://osf.io/jxy9z. Source data are provided with this paper.

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Acknowledgements

This study was supported in part by a Susan G. Komen Foundation Career Catalyst Research Grant (CCR19605871) and a National Cancer Institute Grant (1K08 CA241070) to W.J., a Department of Defense Grant (W81XWH-19-1-0325) to B.Y.S.K. and a Cancer Center Support (Core) Grant (P30 CA016672) from the National Cancer Institute, National Institutes of Health, to The University of Texas MD Anderson Cancer Center (PI: P. W. Pisters). The authors thank C. Wogan of the Division of Radiation Oncology, MD Anderson Cancer Center, for editorial assistance.

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  1. These authors contributed equally: Yifei Lu, Kristin Huntoon, DaeYong Lee, Yifan Wang.

Authors and Affiliations

  1. Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Yifei Lu, Kristin Huntoon, DaeYong Lee, Yaqing Qie, Thomas D. Gallup, Hai Zhao & Betty Y. S. Kim

  2. Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Yifei Lu, Kristin Huntoon, DaeYong Lee, Yaqing Qie, Hai Zhao & Betty Y. S. Kim

  3. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Yifan Wang, JongHoon Ha, Xuefeng Li, Benjamin R. Schrank, Shiyan Dong, Minjeong Kang, Zhaogang Yang, Jing Li & Wen Jiang

  4. Department of Therapeutic Radiology, Yale New Haven Hospital, New Haven, CT, USA

    Yi An

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Contributions

Y.L., W.J. and B.Y.S.K. conceived the study and designed the experiments. Y.L., K.H., D.L. and Y.Q. performed the experiments and generated the data. Y.L., K.H., W.J. and B.Y.S.K. analysed the data and interpreted the results. All authors helped to write the paper.

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Correspondence to Betty Y. S. Kim or Wen Jiang.

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Competing interests

The University of Texas MD Anderson Cancer Center has filed a patent application on the technology and intellectual property reported here for which Y.L., K.H., W.J. and B.Y.S.K are inventors. The remaining authors declare no competing interests.

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Lu, Y., Huntoon, K., Lee, D. et al. Immunological conversion of solid tumours using a bispecific nanobioconjugate for cancer immunotherapy. Nat. Nanotechnol. 17, 1332–1341 (2022). https://doi.org/10.1038/s41565-022-01245-7

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