USE OF CAR-T CELLS AS A TREATMENT FOR MENINGIOMA: AN INTEGRATIVE REVIEW

Meningioma is the most prevalent primary tumor of the central nervous system (CNS), typically located outside the blood-brain barrier, favoring the use of immunotherapies. In addition, morbidity results from the tumor mass effect rather than from diffuse infiltration of the adjacent cerebral parenchyma. As a consequence, Chimeric antigen receptor (CAR) T cells seem promising due to their specificity and less invasive procedure. CAR-T cells are genetically engineered to express an extracellular antigen recognition moiety, composed by 2 variable regions of a monoclonal antibody, connected by a linker that recognizes a tumor cell-surface protein without the need of a specific HLA. To conduct an integrative review to synthesize the recent available evidence on the use of CAR-T cell therapy for the treatment of meningiomas. A search was performed using the PubMed and Virtual Health Library (BVS) databases with the following keywords: (((car-t cell therapy)) OR ((Chimeric Antigen Receptor T-cell therapy))) AND ((meningioma)). The inclusion criteria were: experimental studies in humans and animals, Case Reports, articles published within the last 10 years, observational studies, full-text available, articles in English or Portuguese. The exclusion criteria were: Case Reports, reviews, articles older than 10 years. Results: At first, 18 articles were found with 14 being doubles. After screening, only 3 were selected. The first article, by Ramapriyan et al., used tissues obtained from humans or animals. Human meningioma cells were implanted in mice, which were randomized to receive UTD, CAR T-CD19, or CAR T-mesothelin. Mesothelin-specific CAR-T cells presented specificity, reduced the tumor, increased target clearance, produced higher levels of IFN-?, TNF, and IL-2 and of immune infiltrated tumor spheroids. The study conducted by Pellegrino et al., used a specific activator targeting SSTR2 referred to as OCTO-FLUO. It coated the cell membrane, without accumulating intracellularly or in the absence of SSTR2. Subsequently, an anti-FITC CAR T cell (AdFITC(E2)-CAR) was generated to interact with Octo-Fluo and only the animals that received both the cells and the peptide showed cellular infiltration and cytokine release. In addition, the group infused with 2.5 nmol exhibited slower action. At last, Tang et al., used tissues from an anaplastic meningioma with overexpression of B7-H3. B7-H3-targeted CAR-T cells presented a specific killing effect against the patient tumor tissues and induced specific antitumor effects, releasing cytotoxic and enzyme-linked immunosorbent assay. MRI results indicated stability in the tumor only near the application with B7-H3 expression decreasing only in the region of CAR-T-cell infiltration, where CAR-T-cell trafficking was limited. The treatment was well-tolerated and was not associated with any toxic effects of grade 3 or higher. The slow progression of this tumor favors treatment strategies based on a single-target approach and even partial tumor volume reduction may provide clinical benefit. In general, this treatment showed low “on-target, off-tumor” toxicity and a highly antigen sensitivity. Although more research must be conducted about this therapy application in animals and humans, CAR T cells therapy shows a viable, efficient and less invasive solution to treat meningiomas.