Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas

Ogino, Hirokazu; Taylor, Jennie; Nejo, Takahide; Gibson, David R.; Watchmaker, Payal; Okada, Kaori; Saijo, Atsuro; Tedesco, Meghan; Shai, Anny; Wong, Cynthia M.; Rabbitt, Jane; Olin, Michael R.; Moertel, Christopher L.; Nishioka, Yasuhiko; Salazar, Andrés M.; Molinaro, Annette M.; Phillips, Joanna J.; Butowski, Nicholas; Clarke, Jennifer; Bush, Nancy Ann Oberheim; Hervey-Jumper, Shawn L.; Theodosopoulos, Philip V.; Chang, Susan M.; Berger, Mitchel S.; Okada, Hideho

doi:10.1172/jci151239

Cited by 41 publications

(24 citation statements)

References 45 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two phase III trials evaluating distinct vaccine approaches for newly diagnosed glioblastoma have been reported. The ACT IV study randomized newly diagnosed glioblastoma patients with EGFRvIII-positive tumors to the standard of care with a placebo or a peptide vaccine to EGFRvIII (NCT01480479) [43 ▪▪ ]. Although nonrandomized studies demonstrated a survival benefit with this vaccine relative to historical controls [41], no improvement in OS was noted in this study.…”

Section: Antitumor Vaccinationmentioning

confidence: 76%

“…OS for this study has not been reported and will require extended follow-up due to the long median OS of patients with low-grade glioma. PFS was 11 months, and there was no difference in PFS between the two arms of the study [43 ▪▪ ].…”

Section: Antitumor Vaccinationmentioning

confidence: 85%

“…Two recently published trials enrolled patients with IDH -mutant grade 3 and 4 astrocytoma and low-grade glioma [42 ▪▪ ,43 ▪▪ ]. These patient populations are in general younger and therefore potentially more capable of stronger immune responses compared with glioblastoma patients, who are typically older.…”

Section: Antitumor Vaccinationmentioning

confidence: 99%

See 2 more Smart Citations

Immunotherapy approaches for adult glioma: knowledge gained from recent clinical trials

Andersen

Reardon

2022

Current Opinion in Neurology

View full text Add to dashboard Cite

Purpose of reviewSummarize principles behind various immunotherapy approaches for high and low-grade glioma in the context of recently completed clinical trials and the new insights they provide.Recent findingsDespite the widespread success of therapies targeting the T-cell checkpoints programmed-death 1 and cytotoxic T lymphocyte antigen 4 in other malignancies, recent phase III trials in glioblastoma confirm the lack of efficacy of anti-programmed-death 1 monotherapy in more than 90% of patients. Vaccination approaches remain under investigation for high-grade glioma and have shown activity in some low-grade glioma patients. Chimeric antigen receptor T cells now feature a new generation of products engineered to potentially withstand glucocorticoid therapy. Oncolytic viral therapies have similarly advanced in sophistication, with drug-sensitive gene expression and tumor-selective modifications. Combinations of therapies hold promise for overcoming the numerous mechanisms of immune suppression in glioma.SummaryAlthough immunotherapies have yet to show rates of efficacy compared with other malignancies, new knowledge of immunology and combination therapies brings hope for improved efficacy in the future.

show abstract

Section: Antitumor Vaccinationmentioning

confidence: 76%

Section: Antitumor Vaccinationmentioning

confidence: 85%

See 1 more Smart Citation

Immunotherapy approaches for adult glioma: knowledge gained from recent clinical trials

Andersen

Reardon

2022

Current Opinion in Neurology

View full text Add to dashboard Cite

show abstract

“…The immune activity and stromal activity were remarkably elevated in the high-risk group, which once again reiterated the heterogeneity of the glioma TIME between the two groups. Determining the roles of the signature genes in TIME cell infiltration heterogeneity will be beneficial to better understand the mechanisms of the TIME antitumor immune response and developing novel immunotherapy strategies ( Kim et al, 2022 ; Ogino et al, 2022 ; Tian et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

et al. 2022

View full text Add to dashboard Cite

Gliomas, a type of primary brain tumor, have emerged as a threat to global mortality due to their high heterogeneity and mortality. A low-grade glioma (LGG), although less aggressive compared with glioblastoma, still exhibits high recurrence and malignant progression. Ubiquitination is one of the most important posttranslational modifications that contribute to carcinogenesis and cancer recurrence. E3-related genes (E3RGs) play essential roles in the process of ubiquitination. Yet, the biological function and clinical significance of E3RGs in LGGs need further exploration. In this study, differentially expressed genes (DEGs) were screened by three differential expression analyses of LGG samples from The Cancer Genome Atlas (TCGA) database. DEGs with prognostic significance were selected by the univariate Cox regression analysis and log-rank statistical test. The LASSO-COX method was performed to identify an E3-related prognostic signature consisting of seven genes AURKA, PCGF2, MAP3K1, TRIM34, PRKN, TLE3, and TRIM17. The Chinese Glioma Genome Atlas (CGGA) dataset was used as the validation cohort. Kaplan–Meier survival analysis showed that LGG patients in the low-risk group had significantly higher overall survival time than those in the high-risk group in both TCGA and CGGA cohorts. Furthermore, multivariate Cox regression analysis revealed that the E3RG signature could be used as an independent prognostic factor. A nomogram based on the E3RG signature was then established and provided the prediction of the 1-, 3-, and 5-year survival probability of patients with LGGs. Moreover, DEGs were analyzed based on the risk signature, on which function analyses were performed. GO and KEGG analyses uncovered gene enrichment in extracellular matrix–related functions and immune-related biological processes in the high-risk group. GSEA revealed high enrichment in pathways that promote tumorigenesis and progression in the high-risk group. Furthermore, ESTIMATE algorithm analysis showed a significant difference in immune and stroma activity between high- and low-risk groups. Positive correlations between the risk signature and the tumor microenvironment immune cell infiltration and immune checkpoint molecules were also observed, implying that patients with the high-risk score may have better responses to immunotherapy. Overall, our findings might provide potential diagnostic and prognostic markers for LGG patients and offer meaningful insight for individualized treatment.

show abstract

“…Recent trials with shared-non-mutated, shared-mutated, and personalized-mutated antigens in peptide + adjuvant forms have been tested, showing safety, an antigen-specific antibody response [ 22 ], sustained memory CD8 + or TH1 CD4 + T cell response against personalized antigen peptides [ 23 ] as well as an association between the development of vaccine-specific CD8 + effector memory cells and median OS [ 24 ]. More recently, a pilot randomized study with pre-surgical vaccinations with GBM stem cell lysate in patients with WHO grade II low-grade glioma demonstrated homing of vaccine-reactive CD8 + T-cell clones and increased tissue resident-like CD8 + T-cells in the surgically resected glioma following the neoadjuvant vaccination [ 25 ].…”

Section: What Is the State Of Io For Brain Tumors In Academia And Non...mentioning

confidence: 99%

The future of cancer immunotherapy for brain tumors: a collaborative workshop

et al. 2022

Self Cite

View full text Add to dashboard Cite

Harnessing the effector mechanisms of the immune system to combat brain tumors with antigen specificity and memory has been in research and clinical testing for many years. Government grant mechanisms and non-profit organizations have supported many innovative projects and trials while biotech companies have invested in the development of needed tools, assays and novel clinical approaches. The National Brain Tumor Society and the Parker Institute for Cancer Immunotherapy partnered to host a workshop to share recent data, ideas and identify both hurdles and new opportunities for harnessing immunotherapy against pediatric and adult brain tumors. Adoptively transferred cell therapies have recently shown promising early clinical results. Local cell delivery to the brain, new antigen targets and innovative engineering approaches are poised for testing in a new generation of clinical trials. Although several such advances have been made, several obstacles remain for the successful application of immunotherapies for brain tumors, including the need for more representative animal models that can better foreshadow human trial outcomes. Tumor and tumor microenvironment biopsies with multiomic analysis are critical to understand mechanisms of response and patient stratification, yet brain tumors are especially challenging for such biopsy collection. These workshop proceedings and commentary shed light on the status of immunotherapy in pediatric and adult brain tumor patients, including current research as well as opportunities for improving future efforts to bring immunotherapy to the forefront in the management of brain tumors.

show abstract

Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas

Cited by 41 publications

References 45 publications

Immunotherapy approaches for adult glioma: knowledge gained from recent clinical trials

Immunotherapy approaches for adult glioma: knowledge gained from recent clinical trials

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

The future of cancer immunotherapy for brain tumors: a collaborative workshop

Contact Info

Product

Resources

About