Chimeric Antigen Receptor Cell Therapy: Overcoming Obstacles to Battle Cancer

Abstract

Chimeric antigen receptors (CAR) are fusion proteins engineered from antigen recognition, signaling, and costimulatory domains that can be used to reprogram T cells to specifically target tumor cells expressing specific antigens. Current CAR-T cell technology utilizes the patient’s own T cells to stably express CARs and has achieved exciting clinical success in the past few years. However, current CAR-T cell therapy still faces several challenges, including suboptimal persistence and potency, impaired trafficking to solid tumors, local immunosuppression within the tumor microenvironment and intrinsic toxicity associated with CAR-T cells. This review focuses on recent strategies to improve the clinical efficacy of CAR-T cell therapy and other exciting CAR approaches currently under investigation, including CAR natural killer (NK) and NKT cell therapies.

Establishment of a novel anti-TROP2 monoclonal antibody TrMab-29 for immunohistochemical analysis

“…RIT is a modality permitting selective internal radiation therapy using radiolabeled mAbs against cancer-associated antigens [ 36 ], whereas near-infrared PIT (NIR-PIT) is a novel cancer therapy that combines the specificity of mAbs with directed toxicity induced by a photoabsorber following exposure to NIR light [ 37 ]. Alternatively, CAR-T therapy enables T-cells to detect predefined surface antigens on cancer cells independent of major histocompatibility restriction [ 38 ]. Following the establishment and characterization of our novel anti-TROP2 mAb described in the current study, we will investigate different treatment modalities, including ADC, RIT, PIT, and CAR-T-cell therapy, to explore TrMab-29-mediated antitumor activities in TROP2-expressing cancers.…”

Trogocytosis between Non-Immune Cells for Cell Clearance, and among Immune-Related Cells for Modulating Immune Responses and Autoimmunity

“…(6) CART immunotherapy may also face several challenges including therapeutic potency, impaired trafficking to solid tumor, local immunosuppression within tumor microenvironment, and toxicity associated with CART cells. Although Petty et al [165] proposed to use CAR-NK or CAR-NKT cell instead of CAR-T cells. Combination therapy of CAR cells and anti-tumor antibody may potentially improve the efficacy for CAR cells trafficking into solid tumors.…”

Targeted Cellular Micropharmacies: Cells Engineered for Localized Drug Delivery

“…CAR T cell benefits can last for many years, with memory CAR T cells observed in various patients at long-term follow up and can be directed to a variety of cell surface targets [41][42][43][44]. However, CAR T cell therapies have not generally been successful for the majority of solid tumors due to the lack of unique TAAs, and inhibition by the immunosuppressive TME [21,45,46], with severe toxicities in some cases [47], and relapse in some patients due to either CAR T cell exhaustion [48,49] or downregulation of the cognate antigen by tumor cells [50].…”