Related Experiment Video
Updated: May 22, 2025
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Unusual Partners: γδ-TCR-Based T Cell Therapy in Combination with Oncolytic Virus Treatment for Diffuse Midline
Konstantinos Vazaios1,2, Patricia Hernández López2, Tineke Aarts-Riemens2
1Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.
Abstract:
Due to the minimal survival benefits of existing therapies for pediatric diffuse midline glioma (DMG) patients, new therapeutic modalities are being investigated. Immunotherapies such as CAR-T cells and oncolytic viruses (OVs) are part of these efforts, as evidenced by the increasing number of clinical trials. αβ T cells engineered with a high-affinity γ9δ2 T-cell receptor (TEGs) are immune cells designed to target metabolic changes in malignant or virally infected cells via BTN2A1 and BTN3A. Because the expression of BTN2A1 and BTN3A can be altered in tumor and infected cells, combining TEGs and OVs could potentially enhance the anti-tumor response. We investigated this hypothesis in the following study. We demonstrate that TEGs can indeed target DMG, which expresses BTN2A1 and BTN3A at varying levels, and that OVs can further enhance the expression of BTN3A-but not BTN2A1-in DMG. Functionally, TEGs killed DMG cell cultures, and this killing was further increased after OV infection of the DMGs with either adenovirus Δ24-RGD or reovirus R124 under suboptimal conditions. However, this additive effect was lost when γ9δ2 TCR-ligand interaction was boosted by pamidronate. This study demonstrates the additive effect of combining OVs and Vγ9Vδ2 TCR-engineered immune cells under suboptimal conditions and supports a combination strategy to enhance the efficacy of both therapeutic modalities.
Insights
New immunotherapies combining engineered T cells (TEGs) and oncolytic viruses (OVs) show promise for treating pediatric diffuse midline glioma (DMG). This combination enhances anti-tumor activity against DMG cells expressing specific targets.
Area of Science:
- Immunotherapy
- Oncology
- Virology
Background:
- Pediatric diffuse midline glioma (DMG) has limited treatment options and poor survival outcomes.
- Immunotherapies, including CAR-T cells and oncolytic viruses (OVs), are emerging as novel therapeutic strategies.
- Engineered T cells (TEGs) targeting BTN2A1 and BTN3A offer a potential approach for cancer treatment.
Purpose of the Study:
- To investigate the potential of combining TEGs and OVs to enhance anti-tumor responses in pediatric DMG.
- To evaluate the expression of BTN2A1 and BTN3A in DMG cells after OV infection.
- To assess the synergistic efficacy of combined TEG and OV therapy against DMG.
Main Methods:
- TEGs were used to target DMG cells expressing BTN2A1 and BTN3A.
- DMG cells were infected with oncolytic viruses (adenovirus Δ24-RGD or reovirus R124).
- The expression of BTN2A1 and BTN3A was analyzed post-OV infection.
- Cytotoxicity assays were performed to evaluate the anti-tumor effects of TEGs alone and in combination with OVs.
- The effect of pamidronate on the combined therapy was assessed.
Main Results:
- TEGs effectively targeted DMG cells expressing BTN2A1 and BTN3A.
- OVs enhanced BTN3A expression, but not BTN2A1, in DMG cells.
- Combined TEG and OV therapy demonstrated an additive anti-tumor effect against DMG cell cultures under suboptimal conditions.
- This additive effect was diminished when γ9δ2 TCR-ligand interaction was boosted with pamidronate.
Conclusions:
- Combining OVs with Vγ9Vδ2 TCR-engineered immune cells (TEGs) shows additive efficacy against pediatric DMG.
- This combination strategy holds potential for improving therapeutic outcomes in DMG patients.
- Further research is warranted to optimize this combined immunotherapeutic approach.
More Related Videos
06:15Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
11:15Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
