Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma

Wheeler, Lee Adam; Manzanera, Andrea G.; Bell, Susan D.; Cavaliere, Robert; McGregor, John M.; Grecula, J.C.; Newton, Herbert B.; Lo, Simon S.; Badie, Behnam; Portnow, Jana; Teh, Bin S.; Trask, Todd; Baskin, David S.; New, Pamela; Aguilar, Laura K.; Aguilar-Córdova, Estuardo; Chiocca, E. Antonio

doi:10.1093/neuonc/now002

Cited by 144 publications

(111 citation statements)

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“…Their ability to replicate serves as an advantage for overcoming the low transduction efficiency and vector loss that can hamper non-replicating viruses [7]. Influential work on nonreplicating viruses that exert their antitumor effect through gene-mediated cytotoxic immunotherapy, such as AdV-tk (aglatimagene besadenovec) + valaciclovir, as proposed by Wheeler et al [14], remains an exciting therapeutic opportunity but falls outside the scope of the current review.…”

Section: Introductionmentioning

confidence: 97%

Oncolytic Virotherapy for the Treatment of Malignant Glioma

et al. 2017

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Malignant glioma is the most common primary brain tumor and carries a grim prognosis, with a median survival of just over 14 months. Given the poor outcomes with standard-of-care treatments, novel treatment strategies are needed. The concept of virotherapy for the treatment of malignant tumors dates back more than a century and can be divided into replication-competent oncolytic viruses and replication-deficient viral vectors. Oncolytic viruses are designed to selectively target, infect, and replicate in tumor cells, while sparing surrounding normal brain. A host of oncolytic viruses has been evaluated in early phase human trials with promising safety results, but none has progressed to phase III trials. Despite the 25 years that has passed since the initial publication of genetically engineered oncolytic viruses for the treatment of glioma, much remains to be learned about the use of this therapy, including its mechanism of action, optimal treatment paradigm, appropriate targets, and integration with adjuvant agents. Oncolytic viral therapy for glioma remains promising and will undoubtedly impact the future of patient care.

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Section: Introductionmentioning

confidence: 97%

Oncolytic Virotherapy for the Treatment of Malignant Glioma

et al. 2017

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“…In one study of 48 patients with malignant gliomas, AdV-tk was injected into the tumor cavity following resection, and subsequently received valcyclovir. Overall survival was extended in the treatment group, particularly in those patients that achieved total gross resection at time of surgery [ 118 ]. In studies that involve prostate cancer, one example included a study of 10 patients who received intraprostatic injection of Adv-tk as neoadjuvant therapy to surgery.…”

Section: Prostatakmentioning

confidence: 99%

Clinical Application of Oncolytic Viruses: A Systematic Review

Cook

Chauhan

2020

IJMS

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Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it was not until the introduction of immune checkpoint inhibitors that we realized the true potential of immunotherapy in combating cancer. Oncolytic viruses are one such immunotherapeutic tool that is currently being explored in cancer therapeutics. We present the most comprehensive systematic review of all oncolytic viruses in Phase 1, 2, and 3 clinical trials published to date. We performed a systematic review of all published clinical trials indexed in PubMed that utilized oncolytic viruses. Trials were reviewed for type of oncolytic virus used, method of administration, study design, disease type, primary outcome, and relevant adverse effects. A total of 120 trials were found; 86 trials were available for our review. Included were 60 phase I trials, five phase I/II combination trials, 19 phase II trials, and two phase III clinical trials. Oncolytic viruses are feverously being evaluated in oncology with over 30 different types of oncolytic viruses being explored either as a single agent or in combination with other antitumor agents. To date, only one oncolytic virus therapy has received an FDA approval but advances in bioengineering techniques and our understanding of immunomodulation to heighten oncolytic virus replication and improve tumor kill raises optimism for its future drug development.

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“…Our published mature phase II data appear to show encouraging, albeit not definite, results in terms of possible efficacy on the basis of the extent of residual tumor burden: the median overall survival (OS) durations for patients who underwent gross total resection were 25.0 and 16.9 months (a difference of 8.1 months) for GMCI/standard of care and standard of care, respectively (hazard ratio 0.59; 95% CI, 0.35-0.998; p = .0492); for patients who underwent subtotal resections, the difference was only 1 month (13.5 vs. 12.5 months for GMCI/standard of care vs. standard of care; p = .4584). 33 To further improve this therapy, we have returned to the laboratory. The current theory is that to be effective, an anticancer immune response by cytotoxic 2016 ASCO EDUCATIONAL BOOK | asco.org/edbook T cells requires removal of immune checkpoint signaling mediated by PD-1/PD-L1, [34][35][36] the CTLA-4/B7 family, 37,38 and other molecules.…”

Section: Viral-and Gene-mediated Immunotherapies For Glioblastomamentioning

confidence: 99%

Current State of Immune-Based Therapies for Glioblastoma

Lim

Weller

Chiocca

2016

American Society of Clinical Oncology Educational Book

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Glioblastoma is one of the most aggressive solid tumors, and, despite treatment options such as surgery, radiation, and chemotherapy, its prognosis remains grim. Novel approaches are needed to improve survival. Immunotherapy has proven efficacy for melanoma, lung cancer, and kidney cancer and is now a focus for glioblastoma. In this article, glioblastoma-mediated immunosuppression will be discussed and two exciting immune approaches, checkpoint inhibitors and viral-based therapies, will be reviewed.

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Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma

Abstract: ClinicalTrials.gov NCT00589875.

Cited by 144 publications

References 49 publications

Oncolytic Virotherapy for the Treatment of Malignant Glioma

Oncolytic Virotherapy for the Treatment of Malignant Glioma

Clinical Application of Oncolytic Viruses: A Systematic Review

Current State of Immune-Based Therapies for Glioblastoma

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