4.6 Article

Engineering immunoproteasome-expressing mesenchymal stromal cells: A potent cellular vaccine for lymphoma and melanoma in mice

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CELL REPORTS MEDICINE
卷 2, 期 12, 页码 -

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CELL PRESS
DOI: 10.1016/j.xcrm.2021.100455

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  1. Dr. JohnR. and Clara M. Fraser Memorial Trust
  2. Terry Fox Foundation
  3. Quebec Breast Cancer Foundation
  4. Goodman Cancer Research Center
  5. McGill University

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Engineered mesenchymal stromal cells (MSC-IPr) exhibit enhanced antigen cross-presentation abilities, leading to potent re-activation of T cell immunity and effective control of tumor growth. The combination with antibodies further enhances the effect, making them suitable for designing universal cell-based cancer vaccines.
Dendritic cells (DCs) excel at cross-presenting antigens, but their effectiveness as cancer vaccine is limited. Here, we describe a vaccination approach using mesenchymal stromal cells (MSCs) engineered to express the immunoproteasome complex (MSC-IPr). Such modification instills efficient antigen cross-presentation abilities associated with enhanced major histocompatibility complex class I and CD80 expression, de novo production of interleukin-12, and higher chemokine secretion. This cross-presentation capacity of MSC-IPr is highly dependent on their metabolic activity. Compared with DCs, MSC-IPr hold the ability to cross-present a vastly different epitope repertoire, which translates into potent re-activation of T cell immunity against EL4 and A20 lymphomas and B16 melanoma tumors. Moreover, therapeutic vaccination of mice with pre-established tumors efficiently controls cancer growth, an effect further enhanced when combined with antibodies targeting PD-1, CTLA4, LAG3, or 4-1BB under both autologous and allogeneic settings. Therefore, MSC-IPr constitute a promising subset of non-hematopoietic antigen-presenting cells suitable for designing universal cell-based cancer vaccines.

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