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Updated: May 30, 2025
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Novel B7-H3 CAR T cells show potent antitumor effects in glioblastoma: a preclinical study
Thananya Inthanachai1,2, Chatikorn Boonkrai3, Tanapati Phakham3
1Medical Microbiology, Interdisciplinary and International Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.
Background:
B7 homolog 3 (B7-H3), an overexpressed antigen across multiple solid cancers, represents a promising target for CAR T cell therapy. This study investigated the expression of B7-H3 across various solid tumors and developed novel monoclonal antibodies (mAbs) targeting B7-H3 for CAR T cell therapy.
Methods:
Expression of B7-H3 across various solid tumors was evaluated using RNA-seq data from TCGA, TARGET, and GTEx datasets and by flow cytometry staining. B7-H3-specific mAbs were developed by immunizing mice with human B7-H3, screening with ELISA, and analyzing kinetics with surface plasmon resonance. These mAbs were used to create second-generation CAR constructs, which were evaluated in vitro and in vivo for their antitumor function.
Results:
We identified four mAb clones from immunized mice, with three demonstrating high specificity and affinity. The second-generation B7-H3 CAR T cells derived from these mAbs exhibited robust cytotoxicity against B7-H3-positive targets and successfully infiltrated and eliminated tumor spheroids in vitro. In a xenograft mouse model of glioblastoma, these CAR T cells, particularly those derived from clone A2H4, eradicated the primary tumor, and effectively controlled rechallenge tumor, resulting in prolonged survival of the xenograft mice. In vivo T cell trafficking revealed high accumulation and persistence of A2H4-derived CAR T cells at the tumor site.
Conclusions:
Our results provide novel B7-H3-targeted CAR T cells with high efficacy, paving the way for clinical translation of solid tumor treatment.
Insights
Novel CAR T cells targeting B7-H3 show potent anti-tumor activity in solid cancers. These engineered T cells effectively eliminate tumors and prolong survival, offering a promising new therapy for patients.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- B7 homolog 3 (B7-H3) is a promising target for CAR T cell therapy due to its overexpression in many solid tumors.
- Current CAR T cell therapies are limited in treating solid malignancies.
Purpose of the Study:
- To investigate B7-H3 expression across diverse solid tumors.
- To develop novel monoclonal antibodies (mAbs) targeting B7-H3.
- To engineer and evaluate B7-H3-specific CAR T cells for solid tumor treatment.
Main Methods:
- B7-H3 expression analysis using TCGA, TARGET, and GTEx datasets and flow cytometry.
- Development of B7-H3-specific mAbs via mouse immunization, ELISA, and surface plasmon resonance.
- Creation and in vitro/in vivo evaluation of second-generation CAR constructs.
Main Results:
- Three high-affinity and specific anti-B7-H3 mAb clones were identified.
- B7-H3 CAR T cells demonstrated potent cytotoxicity against B7-H3-positive targets and eradicated tumor spheroids in vitro.
- CAR T cells, particularly A2H4 clone, eradicated glioblastoma xenografts, controlled tumor recurrence, and improved survival in mice.
Conclusions:
- Novel B7-H3-targeted CAR T cells exhibit significant efficacy against solid tumors.
- These findings support the clinical translation of B7-H3 CAR T cells for treating solid malignancies.
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