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Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.

ABSTRACT: With recent advances, chimeric antigen receptor (CAR) immunotherapy has become a promising modality for patients with refractory cancer diseases. The successful results of CAR T cell therapy in relapsed and refractory B-cell malignancies shifted the paradigm of cancer immunotherapy by awakening the scientific, clinical, and commercial interest in translating this technology for the treatment of solid cancers. This review elaborates on fundamental principles of CAR T cell therapy (development of CAR construct, challenges of CAR T cell therapy) and its application on solid tumors as well as CAR T cell therapy potential in the field of neuro-oncology. Glioblastoma (GBM) is identified as one of the most challenging solid tumors with a permissive immunological milieu and dismal prognosis. Standard multimodal treatment using maximal safe resection, radiochemotherapy, and maintenance chemotherapy extends the overall survival beyond a year. Recurrence is, however, inevitable. GBM holds several unique features including its vast intratumoral heterogeneity, immunosuppressive environment, and a partially permissive anatomic blood-brain barrier, which offers a unique opportunity to investigate new treatment approaches. Tremendous efforts have been made in recent years to investigate novel CAR targets and target combinations with standard modalities for solid tumors and GBM to improve treatment efficacy. In this review, we outline the history of CAR immunotherapy development, relevant CAR target antigens validated with CAR T cells as well as preclinical approaches in combination with adjunct approaches via checkpoint inhibition, bispecific antibodies, and second-line systemic therapies that enhance anticancer efficacy of the CAR-based cancer immunotherapy.

SUBMITTER: Yoo HJ

PROVIDER: S-EPMC8580929 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose of reviewOptic neuropathies refer to a collection of diseases in which retinal ganglion cells (RGCs), the specialized neuron of the retina whose axons make up the optic nerve, are selectively damaged. Blindness secondary to optic neuropathies is irreversible as RGCs do not have the capacity for self-renewal and have a limited capacity for self-repair. Numerous strategies are being developed to either prevent further RGC degeneration or replace the cells that have degenerated. In this review, we aim to discuss known limitations to regeneration in central nervous system (CNS), followed by a discussion of previous, current, and future strategies for optic nerve neuroprotection as well as approaches for neuro-regeneration, with an emphasis on developments in the past two years.Recent findingsNeuro-regeneration in the CNS is limited by both intrinsic and extrinsic factors. Environmental barriers to axon regeneration can be divided into two major categories: failure to clear myelin and formation of glial scar. Although inflammatory scars block axon growth past the site of injury, inflammation also provides important signals that activate reparative and regenerative pathways in RGCs. Neuroprotection with neurotrophins as monotherapy is not effective at preventing RGC degeneration likely secondary to rapid clearance of growth factors. Novel approaches involve exploiting different technologies to provide sustained delivery of neurotrophins. Other approaches include application of anti-apoptosis molecules and anti-axon retraction molecules. Although stem cells are becoming a viable option for generating RGCs for cell-replacement-based strategies, there are still many critical barriers to overcome before they can be used in clinical practice. Adjuvant treatments, such as application of electrical fields, scaffolds, and magnetic field stimulation, may be useful in helping transplanted RGCs extend axons in the proper orientation and assist with new synapse formation.SummaryDifferent optic neuropathies will benefit from neuro-protective versus neuro-regenerative approaches. Developing clinically effective treatments for optic nerve disease will require a collaborative approach that not only employs neurotrophic factors but also incorporates signals that promote axonogenesis, direct axon growth towards intended targets, and promote appropriate synaptogenesis.

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Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.

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