Abstract Recurrent glioblastoma (rGBM) is an aggressive malignant brain tumor, with a median survival of 6 months. rGBM establishes an immunosuppressive tumor microenvironment (TME) driven by regulatory T cells (Treg) and exhausted T cells (Tex). Since both Treg and Tex highly express CTLA4, antagonistic CTLA4 antibodies (αCTLA4) were considered promising therapeutic agents. Despite this rationale, clinical trials showed no survival benefit in rGBM, likely due to poor tumor penetration of αCTLA4. Therefore, technology to enhance αCTLA4 delivery in rGBM tissue is critically needed. rGBM acquires treatment resistance through alteration of extracellular matrix (ECM) proteins in the tumor microenvironment (TME). Our lab proposes utilizing this ECM change as a reservoir to accumulate αCTLA4. We focused on COL I Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4045.
Barr et al. (Fri,) studied this question.