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

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 prox-imal 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 indi-vidual 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 overcom-ing 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.