Local Immune-Triggered Surface-Modified Stem Cells for Solid Tumor Immunotherapy

Here, described are additional treatment strategies that make use of human mesenchymal stem cell (hMSC)-based local immunotherapeutic agents for the treatment of solid tumors. Dibenzocyclooctyne-poly(ethylene glycol)-pheophorbide A conjugates are engineered for cell surface conjugation by copper-free click chemistry and are subsequently conjugated to hMSC (hMSC-DPP). hMSC-DPP can recognize and migrate toward cancer lesions, where they secrete pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, and heat shock protein 70 in pursuance of photodynamic therapy-mediated cell death. The secreted immune factors trigger interferon gamma, IL-2, IL-4, IL-12, and granulocyte-macrophage colony-stimulating factor, resulting in the local accumulation of T cells, B cells, natural killer cells, and antigen presenting cells at the tumor site. Treatment with hMSC-DPP induces the accumulation of cytokines at the cancer site and minimizes systemic immune-based side effects. This strategy is expected to increase the vulnerability of cancer cells to immune cells and cytokines, thus aiding in the development of a robust treatment platform for cancer immunotherapy.