Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC

Cloughesy, Timothy F.; Landolfi, Joseph C.; Vogelbaum, Michael A.; Ostertag, Derek; Elder, J. Bradley; Bloomfield, Stephen M.; Carter, Bob S.; Chen, Clark C.; Kalkanis, Steven N.; Kesari, Santosh; Lai, Albert; Lee, Ian Y.; Liau, Linda M.; Mikkelsen, Tom; Nghiemphu, Phioanh L.; Piccioni, David; Accomando, William P.; Diago, Oscar R.; Hogan, Daniel J.; Gammon, Dawn; Kasahara, Noriyuki; Kheoh, Thian; Jolly, Douglas J.; Gruber, Harry E.; Das, Asha; Walbert, Tobias

doi:10.1093/neuonc/noy075

Cited by 146 publications

(113 citation statements)

References 46 publications

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“…On the basis of these trials, clinical trials of combination treatments with GM-CSF with EGFRvIII peptide vaccine and bevacizumab have shown that this combination improved progression-free survival in GBM patients compared with single-modality treatment [135]. Similarly, the preliminary results of a phase II clinical trial of combination treatment with GM-CSF with cyclophosphamide and bevacizumab, as well as results from a phase I trial of combination treatment with MK-1454 (stimulator of IFN gene agonist) and pembrolizumab, and results from a completed trial of Toca 511 and Toca FC, have shown that these treatments increased survival rates in GBM patients [136,137].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

Khan

Mittal

McGee

et al. 2020

IJMS

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Recent efforts in brain tumor research have been directed towards the modulation of the immune system for therapeutic interventions. Several human cancers, including gliomas, are infiltrated with immune cell types—including neutrophils and myeloid-derived suppressor cells—that contribute to tumor progression, invasiveness, and treatment resistance. The role of tumor-associated neutrophils and myeloid-derived suppressor cells in cancer biology remains elusive, as these cells can exert a multitude of pro-tumor and antitumor effects. In this review, we provide the current understanding and novel insights on the role of neutrophils and myeloid-derived suppressor cells in glioma progression and treatment resistance, as well as the mechanisms of pleiotropic behaviors in these cells during disease progression, with an emphasis on possible strategies to reprogram these cells towards their antitumor actions.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

Khan

Mittal

McGee

et al. 2020

IJMS

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“…However, either or both TTFields or proton boost may have contributed to this patient's good clinical outcome. Complete radiological responses were observed in other clinical trials, too (25). However, these results should be interpreted with caution and should not be generalized.…”

Section: Evaluation Of Treatment Responsementioning

confidence: 80%

Case Report of Complete Radiological Response of a Thalamic Glioblastoma After Treatment With Proton Therapy Followed by Temozolomide and Tumor-Treating Fields

et al. 2020

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Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. We present a case of a 42-year-old male patient presenting with headache and vomiting. Imaging demonstrated obstructive hydrocephalus and a ring-enhancing lesion in the right posterior thalamus. After endoscopic third ventriculostomy and stereotactic biopsy, the histopathologic diagnosis of a malignant glioma was confirmed by DNA methylation array as GBM isocitrate dehydrogenase wild type. The patient was treated with combined treatment of chemoradiation with temozolomide (TMZ) including proton boost, TMZ maintenance, and tumor-treating fields. In this case report, complete radiological response was observed 1 year after the end of radiation therapy.

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“…Its strategy involves reprogramming retroviruses into vectors that deliver to tumours the gene that encodes the enzyme cytosine deaminase, which converts the harmless compound 5-fluorocytosine into a tumour-cell-killing derivative. In a phase I study 7 , the vector Toca 511 essentially eliminated detectable cancer in more than 20% of recipients. Liau says that although the vectordrug combination alone can kill tumour cells, experiments in animals have shown that a working immune system is crucial for achieving sustained control of the tumour's growth.…”

Section: Awakening the Sleepersmentioning

confidence: 99%

Immunotherapy offers a promising bet against brain cancer

Eisenstein¹

2018

Nature

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he stars seemed to be aligned for rindopepimut in 2015. A trio of clinical studies had indicated strongly that this peptide-based vaccine elicited an immune response that could meaningfully delay the progression of glioblastoma multiforme (GBM), the most aggressive form of brain cancer. The vaccine's manufacturer, Celldex Therapeutics of Hampton, New Jersey, lobbied the US Food and Drug Administration for accelerated approval on the basis of phase II data but the agency demurred, preferring to wait for the results of a phase III trial. Unfortunately, that trial was a failure. An interim analysis of the data in early 2016 indicated no improvement in the survival of people with GBM who received the vaccine, and Celldex terminated its development. Patients and clinicians were deeply disappointed, but not necessarily surprised. "Neuro-oncologists tend to be nihilistic in a lot of ways, just because we have seen so many treatments come and go, " says E. Antonio Chiocca, neurosurgeonin-chief at Brigham and Women's Hospital in Boston, Massachusetts. GBM is also the most common form of brain cancer, accounting for around 50% of primary malignancies, and these tumours are almost always fatal. Surgery, chemotherapy and radiotherapy offer only short-term respite to those affected. The treatment of other tough-totackle cancers, including melanomas, has been Neurosurgeon John Sampson places a treatment-infusing catheter into the brain of a patient with glioblastoma multiforme.

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Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC

Cited by 146 publications

References 46 publications

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

Case Report of Complete Radiological Response of a Thalamic Glioblastoma After Treatment With Proton Therapy Followed by Temozolomide and Tumor-Treating Fields

Immunotherapy offers a promising bet against brain cancer

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