CAR‐Ts: new perspectives in cancer therapy

• Published in: FEBS letters Vol. 596; no. 4; pp. 403 - 416
• Main Authors: Abrantes, Rafaela, Duarte, Henrique O., Gomes, Catarina, Wälchli, Sébastien, Reis, Celso A.
• Format: Journal Article
• Language: English
• Published: England 01.02.2022
• Subjects: Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Binding Sites; cancer; Carbohydrate Sequence; CAR‐T; cell therapy; chimeric antigen receptor; Genetic Engineering - methods; glycans; Glycosylation; Humans; Immunotherapy, Adoptive - methods; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - therapy; Polysaccharides - chemistry; Polysaccharides - immunology; Protein Binding; Protein Domains; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Receptors, Chimeric Antigen - genetics; Receptors, Chimeric Antigen - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; tumour therapy; glycans; tumour therapy; CAR-T; cell therapy; glycosylation; cancer; chimeric antigen receptor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.14270

Chimeric antigen receptor (CAR)‐T‐cell therapy is a promising anticancer treatment that exploits the host's immune system to fight cancer. CAR‐T cell therapy relies on immune cells being modified to express an artificial receptor targeting cancer‐specific markers, and infused into the patients where they will recognize and eliminate the tumour. Although CAR‐T cell therapy has produced encouraging outcomes in patients with haematologic malignancies, solid tumours remain challenging to treat, mainly due to the lack of cancer‐specific molecular targets and the hostile, often immunosuppressive, tumour microenvironment. CAR‐T cell therapy also depends on the quality of the injected product, which is closely connected to CAR design. Here, we explain the technology of CAR‐Ts, focusing on the composition of CARs, their application, and limitations in cancer therapy, as well as on the current strategies to overcome the challenges encountered. We also address potential future targets to overcome the flaws of CAR‐T cell technology in the treatment of cancer, emphasizing glycan antigens, the aberrant forms of which attain high tumour‐specific expression, as promising targets for CAR‐T cell therapy. Chimeric antigen receptor (CAR)‐T cell therapy exploits the host's immune system to fight cancer: it entails immune cells being modified to express an artificial receptor targeted against cancer‐specific markers and then infused into patients, where they will recognize and eliminate tumour cells. This review describes the CAR‐T technology and its application in cancer therapy, highlighting glycoproteins and glycans expressed in cancer cells as novel potential targets.