Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours

SIMPLE SUMMARY: Using immune cells to treat cancers is a promising new approach for leukemias and lymphomas. However, the use of cellular therapy in solid tumours is compromised by poor migration to the tumour, the physical barriers to infiltration, and the active suppression by the tumour. We will review both past and emerging strategies that could be used to enhance the migration and infiltration of adoptively transferred cell types, including CAR NK and T cells, in solid tumour immunotherapy. ABSTRACT: The precision guiding of endogenous or adoptively transferred lymphocytes to the solid tumour mass is obligatory for optimal anti-tumour effects and will improve patient safety. The recognition and elimination of the tumour is best achieved when anti-tumour lymphocytes are proximal to the malignant cells. For example, the regional secretion of soluble factors, cytotoxic granules, and cell-surface molecule interactions are required for the death of tumour cells and the suppression of neovasculature formation, tumour-associated suppressor, or stromal cells. The resistance of individual tumour cell clones to cellular therapy and the hostile environment of the solid tumours is a major challenge to adoptive cell therapy. We review the strategies that could be useful to overcoming insufficient immune cell migration to the tumour cell mass. We argue that existing ‘competitive’ approaches should now be revisited as complementary approaches to improve CAR T and NK cell therapy.