Immunotherapy for Glioblastoma: Adoptive T-cell Strategies.

Glioblastoma (GBM) is a devastating disease with an extremely poor prognosis. Immunotherapy via adoptive cell transfer (ACT), especially with T cells engineered to express chimeric antigen receptors (CAR), represents a particularly promising approach. Despite the recent success of CAR T cells for blood cancers, the question remains whether this powerful anticancer therapy will ultimately work for brain tumors, and whether the primary immunologic challenges in this disease, which include antigenic heterogeneity, immune suppression, and T-cell exhaustion, can be adequately addressed. Here, we contextualize these concepts by reviewing recent developments in ACT for GBM, with a special focus on pioneering clinical trials of CAR T-cell therapy.

Choi BD ，Maus MV ，June CH ，Sampson JH ... -  《-》

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

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

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 cells for brain tumors: Lessons learned and road ahead.

Malignant brain tumors, including glioblastoma, represent some of the most difficult to treat of solid tumors. Nevertheless, recent progress in immunotherapy, across a broad range of tumor types, provides hope that immunological approaches will have the potential to improve outcomes for patients with brain tumors. Chimeric antigen receptors (CAR) T cells, a promising immunotherapeutic modality, utilizes the tumor targeting specificity of any antibody or receptor ligand to redirect the cytolytic potency of T cells. The remarkable clinical response rates of CD19-targeted CAR T cells and early clinical experiences in glioblastoma demonstrating safety and evidence for disease modifying activity support the potential of further advancements ultimately providing clinical benefit for patients. The brain, however, is an immune specialized organ presenting unique and specific challenges to immune-based therapies. Remaining barriers to be overcome for achieving effective CAR T cell therapy in the central nervous system (CNS) include tumor antigenic heterogeneity, an immune-suppressive microenvironment, unique properties of the CNS that limit T cell entry, and risks of immune-based toxicities in this highly sensitive organ. This review will summarize preclinical and clinical data for CAR T cell immunotherapy in glioblastoma and other malignant brain tumors, including present obstacles to advancement.

Akhavan D ，Alizadeh D ，Wang D ，Weist MR ，Shepphird JK ，Brown CE ... -  《-》

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 《-》