Review of the CAR-T Cell Therapy inGlioblastoma

Today, there are numerous cancer treatment options available,including radiotherapy, chemotherapy, etc. CAR-T cell therapyis a remarkable medical technique for obtaining T cells, whichare immune cells engineered in the lab to combat cancer cells.Glioblastoma (GBM) is a solid and hostile tumor that has developedinto a potential target for CAR-T therapy despite therisks involved. This method has been fruitful in the treatmentof many cancerous tumors, but currently, this treatment methodfor treating glioblastoma tumors is associated with advantagesand challenges.Introduction: Glioblastoma is a kind of aggressive and malignantbrain tumor that originates from the glial cells in the brain.It is the most common primary tumor in adults, with low survival and poor prognosis. Among the therapeutic methods in thetreatment of this lesion, one particular immunotherapy is CARTtherapy. The process of this treatment involves entails triggeringthe expression of a customized chimeric antigen receptorthat can selectively recognize and attack a specific antigen inGBM. The antigen receptors of this therapy have five generations,The first generation of these receptors has CD۳-Z in theintercellular domains, which originate from T cells; the secondand third generations have CD۲۸-۴۱BB as auxiliary domains,which cause T cell proliferation and stability. This therapy involvesinducing the expression of a chimeric antigen receptor,which is engineered to target a specific antigen of interest, onautologous T cells, As several of the most common antigens,we can mention EGFR, HER۲, and IL۱۳Rα۲. For instance,IL۱۳Rα۲ is expressed in numerous solid tumors, While it mayappear that incorporating as much as ۵۰–۸۰% of GBM cells,along with B۷-H۳, an antigen that is overexpressed in overhalf of GBM samples and therefore a promising target, couldbe effective, The absence of tumor-specific antigen expressionand low tumor mutational burden severely impede T cell-basedtreatments for GBM, Another barrier that may stop T cells fromreaching the tumor is the extracellular matrix surrounding thetumor cells.Methods: We explored the Google Scholar and PubMed databases,then chose about ۲۰ articles published between April۲۰۲۰ and March ۲۰۲۳ that are related to our subject and keywords.Results: According to the limitations of common treatmentmethods, alternative treatment approaches are necessary to addressthe specific challenges presented by GBM, such as theearly microscopic spread of tumor cells, compromised immunologicalresponse, and risk of toxicity, as well as the limitationsposed by the BBB to drug delivery. Solid tumors are ableto inhibit the immune response and turn off T cells before theycan take effect. Moreover, the efficiency or activity of T cellsexposed to an antigen over an extended period of time may becompromised, and the expression of inhibitory receptors knownas checkpoints may rise.Conclusion: Despite some limitations, These cells can trafficinto the CNS, annihilate tumor cells with precision, decreaseside effects, and minimize collateral damages, In fact, this treatmentmethod was promising for patients.

کلیدواژه ها:

CAR-T cell ، Glioblastoma ، Cell therapy ، Antigen