The Great War of Today: Modifications of CAR-T Cells to Effectively Combat Malignancies.

Immunotherapy of cancer had its early beginnings in the times when the elements of the immune system were still poorly characterized. However, with the progress in molecular biology, it has become feasible to re-engineer T cells in order to eradicate tumour cells. The use of synthetic chimeric antigen receptors (CARs) helped to re-target and simultaneously unleash the cytotoxic potential of T cells. CAR-T therapy proved to be remarkably effective in cases of haematological malignancies, often refractory and relapsed. The success of this approach yielded two Food and Drug Administration (FDA) approvals for the first "living drug" modalities. However, CAR-T therapy is not without flaws. Apart from the side effects associated with the treatment, it became apparent that CAR introduction alters T cell biology and the possible therapeutic outcomes. Additionally, it was shown that CAR-T approaches in solid tumours do not recapitulate the success in the haemato-oncology. Therefore, in this review, we aim to discuss the recent concerns of CAR-T therapy for both haematological and solid tumours. We also summarise the general strategies that are implemented to enhance the efficacy and safety of the CAR-T regimens in blood and solid malignancies.