Chimeric Antigen Receptor T-Cell Therapy: Updates in Glioblastoma Treatment.

Glioblastoma multiforme (GBM) are the most common and among the deadliest brain tumors in adults. Current mainstay treatments are insufficient to treat this tumor, and therefore, more effective therapies are desperately needed. Immunotherapy, which takes advantage of the body's natural defense mechanism, is an exciting emerging field in neuro-oncology. Adoptive cell therapy with chimeric antigen receptor (CAR) T cells provides a treatment strategy based on using patients' own selected and genetically engineered cells that target tumor-associated antigens. These cells are harvested from patients, modified to target specific proteins expressed by the tumor, and re-introduced into the patient with the goal of destroying tumor cells. Here, we review the history of CAR T-cell therapy, and describe the characteristics of various generations of CAR T therapies, and the challenges inherent to treatment of GBM. Finally, we describe recent and current CAR T clinical trials designed to combat GBM.

Feldman L ，Brown C ，Badie B 《-》

Current progress in chimeric antigen receptor T cell therapy for glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors with an unfavorable prognosis and overall survival of approximately 20 months following diagnosis. The current treatment for GBM includes surgical resections and chemo- and radiotherapeutic modalities, which are not effective. CAR-T immunotherapy has been proven effective for CD19-positive blood malignancies, and the application of CAR-T cell therapy for solid tumors including GBM offers great hope for this aggressive tumor which has a limited response to current treatments. CAR-T technology depends on the use of patient-specific T cells genetically engineered to express specific tumor-associated antigens (TAAs). Interaction of CAR-T cells with tumor cells triggers the destruction/elimination of these cells by the induction of cytotoxicity and the release of different cytokines. Despite the great promise of CAR-T cell-based therapy several challenges exist. These include the heterogeneity of GBM cancer cells, aberrant various signaling pathways involved in tumor progression, antigen escape, the hostile inhibitory GBM microenvironment, T cell dysfunction, blood-brain barrier, and defective antigen presentation. All need to be addressed before full application at the clinical level can begin. Herein we provide a focused review of the rationale for the use of different types of CAR-T cells (including FcγRs), the different GBM-associated antigens, the challenges still facing CAR-T-based therapy, and means to overcome such challenges. Finally, we enumerate currently completed and ongoing clinical trials, highlighting the different ways such trials are designed to overcome specific problems. Exploitation of the full potential of CAR-T cell therapy for GBM depends on their solution.

Marei HE ，Althani A ，Afifi N ，Hasan A ，Caceci T ，Pozzoli G ，Cenciarelli C ... -  《Cancer Medicine》

Chimeric Antigen Receptor (CAR) T Cell Therapy for Glioblastoma.

Glioblastoma (GBM) are the most common and aggressive primary brain tumors in adults. Current mainstay treatments include surgery, chemotherapy, and radiation; however, these are ineffective. As a result, immunotherapy treatment strategies are being developed to harness the body's natural defense mechanisms against gliomas. Adoptive cell therapy with chimeric antigen receptor (CAR) T cells uses patients' own T cells that are genetically modified to target tumor-associated antigens. These cells are harvested from patients, engineered to target specific proteins expressed by the tumor and re-injected into the patient with the goal of destroying tumor cells. In this mini review, we outline the history of CAR T cell therapy, describe current antigen targets, and review challenges this treatment faces specifically in targeting GBM.

Feldman L ，Brown C ，Badie B 《-》

Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future.

Glioblastoma (GBM) is a highly aggressive glioma with an extremely poor prognosis after conventional treatment. Recent advances in immunotherapy offer hope for these patients with incurable GBM. Our present review aimed to provide an overview of immunotherapy for GBM, especially chimeric antigen receptor T-cell (CAR T) therapy. CAR T-cell immunotherapy, which involves the engineering of T cells to kill tumors by targeting cell surface-specific antigens, has been successful in eliminating B-cell leukemia by targeting CD19. IL-13Rα2, EGFRvIII, and HER2-targeted CAR T cells have shown significant clinical efficacy and safety in phase 1 or 2 clinical trials conducted in patients with GBM; these findings support the need for further studies to examine if this therapy can ultimately benefit this patient group. However, local physical barriers, high tumor heterogeneity, and antigen escape make the use of CAR T therapy, as a treatment for GBM, challenging. The potential directions for improving the efficacy of CAR T in GBM are to combine the existing traditional therapies and the construction of multi-target CAR T cells.

Li L ，Zhu X ，Qian Y ，Yuan X ，Ding Y ，Hu D ，He X ，Wu Y ... -  《Frontiers in Immunology》

CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges.

Bagley SJ ，Desai AS ，Linette GP ，June CH ，O'Rourke DM ... -  《-》