Fig. 2
From: Recent advances and future challenges of tumor vaccination therapy for recurrent glioblastoma
Major available immunotherapies for newly diagnosed and recurrent glioblastoma. A Treatment of monoclonal antibodies. There are three phase III clinical trials involving immune checkpoint inhibitors on GBM, namely CheckMate143 in rGBM, CheckMatre498 in uMGMT nGBM and CheckMate548 in MGMT nGBM. However, all the three clinical trials failed to prolong OS of nGBM/rGBM. B Treatment of oncolytic virus/vectors. Virus potentially releases neoantigen and modulates damage-associated molecular patterns, it also helps to deliver gene therapy and release key inflammatory factors to activate immune system. Herpesviruses, reoviruses, pox virus, adenoviruses and Zika viruses are commonly used in vaccines in clinical manner. Briefly, virus vaccines and vectors have showed favorable anti-tumor activity in preclinical models and small clinical trials. C Treatment of chimeric antigen receptor. Chimeric antigen receptor (CAR) therapies mainly include CAR-T, TCR-T and CAR-NK. Common CAR-T targets involve EGFR vIII, HER2, IL-13αR2, NKG2D etc., common CAR-NK targtes involve NKG2D, glioma stem cell etc. CAR therapies demonstrate promising efficacy in preclinical glioma models, the large-scale clinical trials are still ongoing. D Treatment of peptide vaccines. EGFR vIII is also regarded as a target for peptide vaccine in glioma, the ACT IV trial administrates Rindopepimut in nGBM, the ReACT trial uses Rindopepimut to treat rGBM. OS of rGBM is prolonged in ReACT trial. E Treatment of DC vaccines. Tumor antigen, stem cell antigen and CMV antigen can be degraded to peptide, distinct peptide will invoke DCs to secrete immune activators to enhance the anti-tumor immunity. After the process by the peptide, sensitive DCs will be selected to generate DC vaccines. A phase III randomized controlled trial conducted on nGBM and rGBM reveales DCVax-L prolongs the OS with acceptable toxicity. F Other novel therapies include nanoparticles therapy, gene therapy and oligonucleotide therapy. The check mark in green indicates OS of glioma patients can be prolonged in clinical trials; the cross in red indicates OS of glioma patients can not be significantly prolonged. PD-1, programmed cell death 1; PD-L1 programmed cell death ligand 1; GBM, glioblastoma; nGBM, newly diagnosed GBM; rGBM, recurrent GBM; uMGMT, MGMT promoter unmethylated; MGMT, MGMT promoter methylated; DCs, dendritic cells; CAR, chimeric antigen receptor; TCR, T cell receptor-T; NK cells, natural killer cells; CMV, cytomegalovirus; OS, overall survival