Prediction of Tumor Development and Urine-Based Liquid Biopsy for Molecule-Targeted Therapy of Gliomas.

The timing of the acquisition of tumor-specific gene mutations and the systems by which these gene mutations are acquired during tumorigenesis were clarified. Advances in our understanding of tumorigenesis are being made every day, and therapies targeting fundamental genetic alterations have great potential for cancer treatment. Moreover, our research team successfully estimated tumor progression using mathematical modeling and attempted early diagnosis of brain tumors. We developed a nanodevice that enables urinary genetic diagnosis in a simple and noninvasive manner. Mainly on the basis of our research and experience, this review article presents novel therapies being developed for central nervous system cancers and six molecules, which upon mutation cause tumorigenesis and tumor progression. Further understanding of the genetic characteristics of brain tumors will lead to the development of precise drugs and improve individual treatment outcomes.

Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47Δ combination therapy against glioblastoma.

Glioblastoma is a devastating malignant brain tumor with a poor prognosis despite standard therapy. Podoplanin (PDPN), a type I transmembrane mucin-like glycoprotein that is overexpressed in various cancers, is a potential therapeutic target for the treatment of glioblastoma. We previously reported the efficacy of chimeric antigen receptor (CAR)-T cells using an anti-pan-PDPN monoclonal antibody (mAb; NZ-1)-based third-generation CAR in a xenograft mouse model. However, NZ-1 also reacted with PDPN-expressing normal cells, such as lymphatic endothelial cells, pulmonary alveolar type I cells, and podocytes. To overcome possible on-target-off-tumor effects, we produced a cancer-specific mAb (CasMab, LpMab-2)-based CAR. LpMab-2 (Lp2) reacted with PDPN-expressing cancer cells but not with normal cells. In this study, Lp2-CAR-transduced T cells (Lp2-CAR-T) specifically targeted PDPN-expressing glioma cells while sparing the PDPN-expressing normal cells. Lp2-CAR-T also killed patient-derived glioma stem cells, demonstrating its clinical potential against glioblastoma. Systemic injection of Lp2-CAR-T cells inhibited the growth of a subcutaneous glioma xenograft model in immunodeficient mice. Combination therapy with Lp2-CAR-T and oncolytic virus G47Δ, a third-generation recombinant herpes simplex virus (HSV)-1, further inhibited the tumor growth and improved survival. These findings indicate that the combination therapy of Lp2-CAR-T cells and G47Δ may be a promising approach to treat glioblastoma.