Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model.

in Cancer immunology, immunotherapy : CII by Tetsuro Tachi, Noriyuki Kijima, Hideki Kuroda, Syunya Ikeda, Koki Murakami, Tomoyoshi Nakagawa, Moto Yaga, Kanji Nakagawa, Reina Utsugi, Ryuichi Hirayama, Yoshiko Okita, Naoki Kagawa, Haruhiko Kishima, Chihaya Imai, Naoki Hosen

TLDR

  • The study found that CAR-T and CAR-NK cells targeting B7-H3 have the potential to eliminate GBM cells. The study's findings suggest that CAR-T and CAR-NK cells targeting B7-H3 may have the potential to eliminate GBM cells. The study's results could lead to the development of novel therapies for GBM.

Abstract

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor for which novel therapies are needed. Recently, chimeric antigen receptor (CAR) T cell therapy has been shown to be effective against GBM, but it is a personalized medicine and requires high cost and long time for the cell production. CAR-transduced natural killer (NK) cells can be used for "off-the-shelf" cellular immunotherapy because they do not induce graft-versus-host disease. Therefore, we aimed to analyze the anti-GBM effect of CAR-T or NK cells targeting B7-H3, which is known to be highly expressed in GBM. CAR-T cells targeting B7-H3 were generated using previously reported anti-B7-H3 scFv sequences. Cord blood (CB)-derived NK cells transduced with the B7-H3 CAR were also generated. Their anti-GBM effect was analyzed in vitro. The antitumor effect of intracranial injection of the B7-H3 CAR-T or NK cells was investigated in an in vivo xenograft model with patient-derived GBM cells. Both B7-H3 CAR-T cells and CAR-NK cells exhibited marked cytotoxicity against patient-derived GBM cells in vitro. Furthermore, intracranial injection of CAR-T cells and CAR-NK cells targeting B7-H3 resulted in a significant antitumor effect against patient-derived GBM xenografts. Not only CAR-T cells but also CB-derived CAR-NK cells targeting B7-H3 may have the potential to eliminate GBM cells.

Overview

  • The study aims to analyze the anti-GBM effect of CAR-T or NK cells targeting B7-H3, which is highly expressed in GBM. The study generates CAR-T cells targeting B7-H3 using previously reported anti-B7-H3 scFv sequences and CB-derived NK cells transduced with the B7-H3 CAR. The anti-GBM effect of these cells is analyzed in vitro and in vivo using patient-derived GBM cells. The study's primary objective is to investigate the potential of CAR-T and CAR-NK cells targeting B7-H3 to eliminate GBM cells.

Comparative Analysis & Findings

  • Both B7-H3 CAR-T cells and CAR-NK cells exhibited marked cytotoxicity against patient-derived GBM cells in vitro. Intracranial injection of CAR-T cells and CAR-NK cells targeting B7-H3 resulted in a significant antitumor effect against patient-derived GBM xenografts. The study found that both CAR-T and CAR-NK cells targeting B7-H3 have the potential to eliminate GBM cells.

Implications and Future Directions

  • The study's findings suggest that CAR-T and CAR-NK cells targeting B7-H3 may have the potential to eliminate GBM cells. The study's results could lead to the development of novel therapies for GBM. Future research could focus on optimizing the production and delivery of CAR-T and CAR-NK cells targeting B7-H3, as well as investigating the safety and efficacy of these cells in clinical trials.
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