CARs and beyond: tailoring macrophage-based cell therapeutics to combat solid malignancies

Recent understanding of the role and contribution of immune cells in disease onset and progression has pioneered the field of immunotherapies. Use of genetic engineering to deliver, correct or enhance immune cells has been clinically successful, especially in the field of cancer immunotherapy. Indeed, one of the most attractive approaches is the introduction of chimeric antigen receptors (CARs) to immune cells, such as T cells. Recent studies revealed that adapting this platform for use in macrophages may widen the spectrum of CAR applications for better control of solid tumors and, thus, extend this treatment strategy to more patients with cancer. Given the novel insights into tumor-associated macrophages and new targeting strategies to boost anticancer therapy, this review aims to provide an overview of the current status of the role of macrophages in cancer therapy. The various genetic engineering approaches that can be used to optimize macrophages for use in oncology are discussed, with special attention dedicated to the implication of the CAR platform on macrophages for anticancer therapy. The current clinical status, challenges and future perspective of macrophage-based drugs are highlighted.