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Hung Trinh: CAR-T cell therapy for the treatment of adult high-grade gliomas

Hung Trinh/LinkedIn

Dec 23, 2024, 21:16

Hung Trinh: CAR-T cell therapy for the treatment of adult high-grade gliomas

Hung Trinh, Senior Director of Business Development at OBiO Tech, shared a post on LinkedIn:

“A comprehensive update and status for CAR-T cell therapy for the treatment of adult high-grade gliomas, Nature Precision Oncology.

Treatment for malignant primary brain tumors, including glioblastoma, remains a significant challenge despite advances in therapy.

CAR-T cell immunotherapy represents a promising alternative to conventional treatments.

This review discusses the landscape of clinical trials for CAR-T cell therapy targeting brain tumors, highlighting key advancements like novel target antigens and combinatorial strategies designed to address tumor heterogeneity and immunosuppression, with the goal of improving outcomes for patients with these aggressive cancers.

Engineering CAR-T cells to overcome the brain tumor microenvironment.

One of the main challenges in treating brain tumors is the immune-suppressive nature of the tumor microenvironment.

Several approaches are being developed to enable the delivery of immune-modulating factors, such as cytokines, directly to the TME.

For example, CAR-T cells engineered to secrete cytokines IL-12 and IL-18 have shown increased activation of surrounding immune cells, such as NK, NKT, and γδ T cells169.

Similarly, CAR-T cells designed to secrete IL-15 have exhibited improved effector functions, elevated levels of the anti-apoptotic protein Bcl-2, decreased expression of PD-1, and superior tumor control and persistence in preclinical GBM models170.

Additionally, CRISPR-Cas9 genome editing techniques have been used to engineer CAR-T cells that resist TGF-β-mediated immunosuppression, a common feature of the GBM tumor microenvironment171.

Also, CAR-T cells have been engineered to prevent the expression of immune checkpoint molecules such as PD-1, which are often upregulated in the TME of GBM and contribute to T cell exhaustion.

By knocking out these checkpoint molecules, CAR-T cells can resist the suppressive signals in the TME, improving their persistence and anti-tumor efficacy172.”

CAR-T cell therapy for the treatment of adult high-grade gliomas

Authors: Sangwoo Park, Marcela V. Maus and Bryan D. Choi.

Hung Trinh

Hung Trinh is the Senior Director of Business Development at OBiO Tech. He previously served as Director of Process Development and Manufacturing Science and Technology at Vyriad and Associate Director of Downstream Process Development at Genezen. With experience in vaccine development, spanning both pre-clinical and clinical studies, Trinh has worked with various CDMOs focusing on lentiviral vector production and CAR-T cell manufacturing