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  • br Challenges in the development of

    2022-09-15


    4.2. Challenges in the development of protocols for human translation
    While a single dose of chemotherapy was optimal to achieve a complete response in mouse models with tumor diameters on the order of 5 mm, larger tumor volumes in patients may require additional cy-cles of treatment. Such activatable delivery systems result in rapid immunogenic cell death and antigen presentation. Therefore, 
    enhancing the proportion of leukocytes, and creating a systemic im-mune response prior to locally-activated chemotherapy is a rational choice. The development of non-invasive methods to assess and track macrophage and T-cell population and activation in patients spatio-temporally over the course of treatment could provide important in-formation for the timing of ADD [49–51]. A major challenge for this field is to translate the use of temperature-sensitive liposomes to the treatment of large animals and humans. The cost of such translational studies required for commercialization has limited the translation and availability of the these activatable nanotherapies.
    5. Conclusions
    We demonstrated that administration of a single dose of activatable chemotherapy effectively reduces tumor viability and induces release of tumor 6-diazo-5-oxo-L-nor-Leucine that are effectively presented by macrophages and DCs. In addition, focal delivery of Dox, which mediates local release of ICD and production of type I IFN, amplifies the signaling pathways to re-lease curative chemokines and cytokines. The resulting local and sys-temic immune stimulation was combined with an immune priming protocol to elicit potent antitumor T-cell responses, thereby exerting robust antitumor efficacy in a murine model of breast cancer. Tumor eradication was observed in both treated and distant tumors of mice treated with the chemo-immunotherapy protocol and 90% of treated mice were tumor-free for 101 days.
    A. Kheirolomoom, et al.
    Conflict of interest
    The authors declare no completing financial of interest.
    Acknowledgements
    This work was supported by funding from National Institute of
    Appendix A. Supplementary data
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