Despite recent advancements in cell-based immunotherapy, there are several obstacles and questions that need to be further investigated and addressed to improve their clinical efficacy in the future. These include, but are not limited to:
- Homing: the anti-tumor cells need to localize to the site of the tumors. How can we properly send the injected immune cells to the tumor site to elicit anti-tumor activity?
- Tumor microenvironment: the tumors may be in a protected niche, surrounded by anti-inflammatory factors that can dampen anti-tumor immune cell function. How can we modify the cells to overcome this immunomodulation?
- Intrinsic immune regulatory mechanisms: After generating an immune response, host regulatory mechanisms are in place to dampen inflammation over time. How can we overcome this to prolong anti-tumor immune responses?
- Target antigen diversity: tumors can express heterogeneous antigen proteins. Can we engineer immune cells to recognize “degenerate” tumor antigens that can overcome this heterogeneity?
- Foreign vs. Self: tumor cells are altered versions of the host cells, so distinction between a tumor vs. healthy host cell may be difficult. How can we ensure that the immune cells only react and eradicate tumors while keeping healthy host cells intact?
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