NeuralCipher Research overview
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Chimeric antigen receptor T (CAR-T) cell therapy has transformed hematologic cancer treatment; however, its application in patients with central nervous system (CNS) involvement remains challenging because of exclusion from key trials. Recent data show that CAR-T cells can breach the blood-brain barrier (BBB) and achieve clinically significant responses in CNS lymphoma, acute lymphoblastic leukemia (ALL), and multiple myeloma (MM). However, limited CNS trafficking, antigen escape, an immunosuppressive microenvironment, and treatment-related neurotoxicity constrain therapeutic efficacy. This review synthesizes recent clinical outcomes, elucidates mechanisms of CNS infiltration and neurotoxicity, and evaluates emerging strategies, including optimized CAR designs, BBB-modulating technologies, alternative delivery routes, and rational combination therapies, to enhance safety and efficacy. Disease-specific nuances, such as Parkinson-like symptoms in CNS myeloma and differential neurotoxicity profiles between primary and secondary CNS lymphomas, are highlighted. By identifying key knowledge gaps and proposing prioritized research directions, this study aims to guide the future translation of CAR-T therapy for CNS hematologic malignancies.
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