Unmet Need
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults and remains one of the most aggressive types of malignancies. The mainstay of GBM treatment is surgery, radiation and adjuvant chemotherapy using temozolomide (TMZ). While treatment options have incrementally improved, survival rates remains dismal. Only 25% of GBM patients survive more than one year, and less than 5% of patients survive more than five years. Consequently, there is a need for novel adjuvant therapies to improve outcomes for GBM patients.
Technology Overview
The inventors have developed a therapeutic approach to improve the efficacy of TMZ therapy in GBM. This approach uses an oral formulation of TMZ and terameprocol (M4N), another chemotherapy drug, to boost the cytotoxic effect of TMZ. This combination chemotherapy was able to halt tumor growth in a mouse model of GBM. Importantly, this enhanced anti-tumor effect was observable even at low concentrations of M4N, at which there is no measurable in vivo cytotoxicity. The inventors also demonstrated that the administration of M4N enhances the titers of specific antitumor antibodies in the sera and promotes the antibody-dependent cell-mediated cytotoxicity of NK cells to suppress tumor growth. Thus, the addition of M4N to a TMZ regimen can boost the anti-tumor activity of TMZ not only through its cytotoxic activity, but also via activation of host humoral immunity.
Stage of Development
The efficacy of this combination chemotherapy has been demonstrated in vivo.
Publications: WO2021108601
