Emerging Trends in CAR Therapy for the Treatment of Cancer: A Literature Review

Abstract

Cancer is the second leading cause of mortality worldwide, accounting for 1 in every 6 deaths over the years of 2020 and 2021. Immunotherapy has emerged as a pivotal treatment for cancer in recent decades. It focuses on engineering the body’s immune system to target and attack cancer cells. Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy that utilizes genetically modified T lymphocytes to produce a specific CAR, enabling them to detect and destroy a patient’s cancer cells possessing the cognate antigen. This therapy has shown to be effective against hematological cancers, but faces challenges in infiltrating solid tumors, toxicity due to excessive cytokine release, and other complications. To address these issues, various immune cells are being investigated for use in CAR therapy against cancer, including macrophages, natural killer cells, dendritic cells, and neutrophils. This literature review reports on new CAR therapies employing different immune cells in the treatment of blood and solid cancers. Clinical studies on CAR immunotherapies for cancer treatment published within the past 5 years (2019-2024) were chosen following multiple advanced searches of the PubMed database. Due to the limited number of clinical trials investigating treatments besides CAR T-cell therapy, the search was expanded to include pre-clinical studies and one ongoing clinical trial. This study's findings revealed that each of the five CAR immune cells examined (T-cells, natural killer cells, macrophages, dendritic cells, and neutrophils) demonstrated significant efficacy in inhibiting cancer growth, with unique benefits and weaknesses depending on cancer type, methods of preparation, additional treatment regimens, and side effects. T-cell and macrophage CAR therapies examined in clinical trials showed similar incidences of adverse events, while CAR natural killer cell therapy demonstrated fewer instances of cytokine release syndrome and neurotoxicity. CAR dendritic cells and neutrophils showed promise as specific carriers of cancer-killing elements, such as chemotherapy drugs or tumoricidal cytokines. Overall, this review underscores the need for further clinical study of CAR natural killer cells and the potential expansion of CAR technologies as tumoricidal instigators and/or targeted carriers of such therapies.