Cancer cells and embryonic tissues share a number of cellular and
molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may
be harnessed to elicit anti-tumor responses in cancer vaccines. RNA-sequencing
revealed that human and murine iPSCs express tumor-associated antigens, and we
show here a proof-of principle for using irradiated iPSCs in autologous
anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor
growth in syngeneic murine breast cancer, mesothelioma, and melanoma models. As
an adjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection
site and reduced metastatic tumor load, which was associated with fewer Th17
cells and increased CD11b+GR1hi myeloid cells.
Adoptive transfer of T cells isolated from vaccine treated-tumor-bearing mice
inhibited tumor growth in unvaccinated recipients, indicating that the iPSC
vaccine promotes an antigen-specific anti-tumor T cell response. Our data
suggest a generalizable strategy for multiple types of cancer that could prove
highly valuable in clinical immunotherapy.
Mesenchymal stem cells (MSCs) have multiple properties including anti-inflammatory and immunomodulatory effects in various disease models and clinical treatments. These beneficial effects, however, are sometimes inconsistent and unpredictable. For wider and proper application, scientists sought to improve MSC functions by engineering. We aimed to invent a novel method to produce synthetic biological drugs from engineered MSCs. We investigated the anti-arthritic effect of engineered MSCs in a collagen-induced arthritis (CIA) model. Biologics such as etanercept are the most successful drugs used in anti-cytokine therapy. Biologics are made of protein components, and thus can be theoretically produced from cells including MSCs. MSCs were transfected with recombinant minicircles encoding etanercept (trade name, Enbrel), which is a tumour necrosis factor α blocker currently used to treat rheumatoid arthritis. We confirmed minicircle expression in MSCs in vitro based on GFP. Etanercept production was verified from the conditioned media. We confirmed that self-reproduced etanercept was biologically active in vitro. Arthritis subsided more efficiently in CIA mice injected with mcTNFR2MSCs than in those injected with conventional MSCs or etanercept only. Although this novel strategy is in a very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics and engineering MSCs.
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