Recent advances and future challenges of tumor vaccination therapy for recurrent glioblastoma

Abstract

Glioblastoma (GBM) is the most malignant CNS tumor with a highest incidence rate, and most patients would undergo a recurrence. Recurrent GBM (rGBM) shows an increasing resistance to chemotherapy and radiotherapy, leading to a significantly poorer prognosis and the urgent need for novel treatments. Immunotherapy, a rapidly developing anti-tumor therapy in recent years, has shown its potential value in rGBM. Recent studies on PD-1 immunotherapy and CAR-T therapy have shown some efficacy, but the outcome was not as expected. Tumor vaccination is the oldest approach of immunotherapies, which has returned to the research focus because of the failure of other strategies and subversive understanding of CNS. The isolation effect of blood brain barrier and the immunosuppressive cell infiltration could lead to resistance existing in all phases of the anti-tumor immune response, where novel tumor vaccines have been designed to overcome these problems through new tumor antigenic targets and regulatory of the systematic immune response. In this review, the immunological characteristics of CNS and GBM would be discussed and summarized, as well as the mechanism of each novel tumor vaccine for rGBM. And through the review of completed early-phase studies and ongoing large-scale phase III clinical trials, evaluation could be conducted for potential immune response, biosecurity and initial clinical outcome, which further draw a panorama of this vital research field and provide some deep thoughts for the prospective tendency of vaccination strategy.

Targeted immunotherapy for glioblastoma involving whole tumor-derived autologous cells in the upfront setting after craniotomy

“…Secondly, monocytes are harvested via leukapheresis and differentiated ex vivo into monocyte-derived dendritic cells (DCs), which are loaded with antigens. Thirdly, tumor antigens are combined in adjuvant formulations [ 29 ].…”

Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment

“…18 Recently, clinical trials have begun on GBM immunotherapy-related drugs which demonstrate durable antitumor activity with acceptable adverse reactions, suggesting that GBM TIME deserves further investigation. 19 Furthermore, m6A methylation promotes or suppresses a variety of tumor pathologies, [20][21][22] but studies on its relationship with GBM are lacking. Therefore, it is intriguing to examine the role of m6A regulators in GBM and their impact on the infiltration of the TIME in GBM.…”

“…Additionally, the progressive decline in neurologic function and quality of life associated with GBM morbidity has a devastating effect on patients, caregivers, and families 18 . Recently, clinical trials have begun on GBM immunotherapy‐related drugs which demonstrate durable antitumor activity with acceptable adverse reactions, suggesting that GBM TIME deserves further investigation 19 . Furthermore, m6A methylation promotes or suppresses a variety of tumor pathologies, 20–22 but studies on its relationship with GBM are lacking.…”

Effective extracellular vesicles in glioma: Focusing on effective ncRNA exosomes and immunotherapy methods for treatment

“…Different types of vaccines are utilized, DC and peptide vaccines are the main techniques used to treat gliomas. Additionally, immune targets of vaccines, such as TAA and TSA, can be utilized to activate adaptive immunity 108–112 . Peptide vaccines are composed of 8–25 amino acids and contain epitopes that serve as antigenic targets.…”