Achieving Graft-Versus-Tumor Effect in Brain Tumor Patients: From Autologous Progenitor Cell Transplant to Active Immunotherapy

Abstract

Success in treating aggressive brain tumors like glioblastoma multiforme and medulloblastoma remains challenging, in part because these malignancies overcome CNS immune surveillance. New insights into brain tumor immunology have led to a rational development of immunotherapeutic strategies, including cytotoxic Tlymphocyte therapies and dendritic cell vaccines. However, these therapies are most effective when applied in a setting of minimal residual disease, so require prior use of standard cytotoxic therapies or cytoreduction by surgery. Myeloablative chemotherapy with autologous hematopoietic cell transplantation (autoHCT) can offer a platform upon which different cellular therapies can be effectively instituted. Specifically, this approach provides an inherent ‘chemical debulking‘ through high-dose chemotherapy and a graft-versus-tumor effect through an autologous T-cell replete graft. Furthermore, autoHCT may be beneficial in ‘resetting‘ the body‘s immune system, potentially ‘breaking‘ tumor tolerance, and in providing a ‘boost‘ of immune effector cells (NK cells or cytotoxic T lymphocytes), which could augment desired anti-tumor effects. As literature on the use of autoHCT in brain tumors is scarce, aspects of immunotherapies applied in non-CNS malignancies are reviewed as potential therapies that could be used in conjunction with autoHCT to eradicate brain tumors.

KEYWORDS::

• brain tumor
• dendritic cell
• glioblastoma multiforme
• graft-versus-tumor
• immunomodulation
• immunotherapy
• medulloblastoma
• mesenchymal stromal cell
• NK cell
• regulatory T cell
• stem cell transplantation

Acknowledgements

The authors would like to thank AY Huang for his thoughtful comments in reviewing the manuscript.

Financial & competing interests disclosure

The authors wish to acknowledge the National Center for Regenerative Medicine at Case Western Reserve University for its research support. A Petrosiute has received funding from the St. Baldrick‘s Foundation. JJ Auletta has received funding from NIH/NIAID AI57801 and the National Center for Regenerative Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors wish to acknowledge the National Center for Regenerative Medicine at Case Western Reserve University for its research support. A Petrosiute has received funding from the St. Baldrick‘s Foundation. JJ Auletta has received funding from NIH/NIAID AI57801 and the National Center for Regenerative Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.