*4.2.3.2 Delivery system*

A major limitation of adoptive T cell therapies is the delivery technology used in the patient. It is noted that the viability and function of the transplanted cells rapidly decline after administration [58]. Hence, different delivery technologies (nanoparticles or scaffolds) have been explored to improve success of ACT. Adjuvant-loaded nanoparticles, chemically conjugated to the surface of T cells to stimulate transplanted cells and minimize the systemic side effects have been designed [59]. Advantages of having a delivery system of T cells which has some immune stimulating mechanisms linked, may help the T cells to enter the tumor site and perform better results of the therapy. Apart from systemic administration route, biomaterials-based strategies have also been explored to locally deliver adoptive T cells to solid tumors [60, 61] as successful targeting of T cells to most solid cancers remain challenging [62]. To overcome the barrier of secluded location of solid tumors, local injection of T cell in brain tumors in mouse model has been tried and has shown better outcome than systemic administration [54].

Overall, biomaterial-mediated local T cell delivery approaches could improve the efficiency of adoptive T cell therapies for treating inoperable solid tumors by overcoming local immunosuppressive barriers. The usefulness of these therapies depends on how quickly T cells can be generated in tumors *in-vivo* using this approach relative to the time it takes to expand T cells *ex-vivo*.
