The Emerging Role of Engineering Immune Cells in Cancer Treatments

Abstract

Cell-based immunotherapy has become one of the forefronts of cancer treatments and led to significant clinical success in multiple refractory/recurrent hematological malignancies. Compared with other conventional treatment approaches, engineered immune cells are considered “living factories” that are able to continually produce anti-tumor factors and have the potential to mediate long-lasting therapeutic benefits following a single application. The intrinsic ability to expand and respond in portion to needs encompasses this technology a greater and more transformative potential to enable a more effective anti-tumor response with less off-target toxicity. Nevertheless, there are still some significant barriers to successfully applying cell-based therapy to treat solid tumors. Five main challenges include restricted trafficking and infiltration, antigen escape and heterogeneity, suboptimal persistence, immunosuppressive tumor microenvironment (TME), and potentially severe side effects and immune-related toxicities. The technological advancement of various biomolecular tools and genetic engineering strategies provides exciting opportunities to address these limitations. In addition, combination therapy that incorporates other treatment modalities within the treatment regimen of cell-based strategy also creates therapeutic synergies that can greatly improve the clinical success of the therapy. This review introduces current observed challenges in treating cancers, with an emphasis on solid malignancies, and discusses some potential engineering solutions that have shown promising results in recent preclinical studies.