Criteria for comparisons and recommendations for a next generation of Chimeric Antigen Receptor (CAR) T cells as HIV-1 treatment

• Main Author: Sabado, Anne Kimberly Bueno
• Format: text
• Language: English
• Published: Animo Repository 2022
• Subjects: Antigens; T cells—Receptors; HIV (Viruses)—Treatment; Biology
• Online Access: https://animorepository.dlsu.edu.ph/etdb_bio/19; https://animorepository.dlsu.edu.ph/cgi/viewcontent.cgi?article=1021&context=etdb_bio
• Institution: De La Salle University

Combination antiretroviral therapy (cART) for Human Immunodeficiency Virus Type 1 (HIV-1) treatment is limited in its ability to target HIV reservoirs that cause a viral rebound in patients. Chimeric antigen receptor (CAR) T cell therapy is a developing treatment to address this issue. Several generations of CAR T cell designs have been released, and this paper summarizes the progression based on published papers. Following designated search terms, a total of 241 journal articles emerged from the initial literature search in reputable electronic databases. The results were filtered by removing 159 non-HIV researches, 12 non-T cell studies, 33 secondary literature, and 7 journals with incomplete information on CAR components. The remaining thirty papers were screened for methodological quality using the JBI Critical Appraisal Checklist for Quasi-Experimental Studies. From the 30 eligible studies, thirteen (13) were first generation CARs, 14 were second generation CARs, and 3 are third generation CARs. Similarities and differences in designs were drawn based on the glycoprotein targets, actions and limitations, lowest effector to target (E:T) ratio, and its corresponding percent (%) specific lysis. Additional components and treatments were summarized. The review suggests a second generation CAR T cell design with CD4 extracellular domain, 4-1BB and CD3ζ intracellular signaling domain, and CD8α hinge and transmembrane domains. The recommended CAR T cell design is formed by analyzing all studies that conducted cytotoxic assay and used additional CAR components and HIV treatment based on three criteria namely targets, actions, and cytotoxicity. The proposed CAR can be used as a reference design to be utilized with other HIV medications, such as antiretroviral therapy, and in constructing better generations of CAR T cells for HIV treatment.