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Updated: Oct 23, 2025
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Treating ICB-resistant glioma with anti-CD40 and mitotic spindle checkpoint controller BAL101553 (lisavanbulin)
Vassilis Genoud1,2, Felipe I Espinoza1, Eliana Marinari1
1Translational Research Center for Hemato-Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Abstract:
Glioblastoma is a highly malignant brain tumor with no curative treatment options, and immune checkpoint blockade has not yet shown major impact. We hypothesized that drugs targeting mitosis might affect the tumor microenvironment and sensitize cancer cells to immunotherapy. We used 2 glioblastoma mouse models with different immunogenicity profiles, GL261 and SB28, to test the efficacy of antineoplastic and immunotherapy combinations. The spindle assembly checkpoint activator BAL101553 (lisavanbulin), agonistic anti-CD40 antibody, and double immune checkpoint blockade (anti-programmed cell death 1 and anti-cytotoxic T lymphocyte-associated protein 4; anti-PD-1 and anti-CTLA-4) were evaluated individually or in combination for treating orthotopic GL261 and SB28 tumors. Genomic and immunological analyses were used to predict and interpret therapy responsiveness. BAL101553 monotherapy increased survival in immune checkpoint blockade-resistant SB28 glioblastoma tumors and synergized with anti-CD40 antibody, in a T cell-independent manner. In contrast, the more immunogenic and highly mutated GL261 model responded best to anti-PD-1 and anti-CTLA-4 therapy and more modestly to BAL101553 and anti-CD40 combination. Our results show that BAL101553 is a promising therapeutic agent for glioblastoma and could synergize with innate immune stimulation. Overall, these data strongly support immune profiling of glioblastoma patients and preclinical testing of combination therapies with appropriate models for particular patient groups.
Insights
The mitosis drug BAL101553 (lisavanbulin) shows promise for glioblastoma, improving survival in resistant models and synergizing with immunotherapy. This highlights the need for personalized glioblastoma treatment strategies.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Cancer Biology
Background:
- Glioblastoma is a deadly brain cancer with limited treatment options.
- Current immune checkpoint blockade therapies have shown minimal impact on glioblastoma.
- Targeting mitosis may alter the tumor microenvironment and enhance immunotherapy response.
Purpose of the Study:
- To evaluate the efficacy of BAL101553 (lisavanbulin) in combination with immunotherapies for glioblastoma.
- To investigate the impact of these combinations on different glioblastoma immunogenicity models.
- To explore genomic and immunological factors influencing treatment response.
Main Methods:
- Utilized two glioblastoma mouse models (GL261 and SB28) with distinct immunogenicity.
- Tested BAL101553, anti-CD40 antibody, and dual immune checkpoint blockade (anti-PD-1/anti-CTLA-4) individually and in combination.
- Performed genomic and immunological analyses to interpret therapy responsiveness.
Main Results:
- BAL101553 monotherapy improved survival in the immune checkpoint blockade-resistant SB28 model.
- BAL101553 synergized with anti-CD40 antibody in a T cell-independent manner in SB28 tumors.
- The immunogenic GL261 model responded best to anti-PD-1/anti-CTLA-4 therapy, with modest benefit from BAL101553 and anti-CD40 combination.
Conclusions:
- BAL101553 is a promising glioblastoma therapeutic agent with potential to synergize with innate immune stimulation.
- Treatment efficacy varies based on glioblastoma immunogenicity and mutational profile.
- Immune profiling and model-specific preclinical testing are crucial for developing effective glioblastoma combination therapies.
