Advances in immunotherapeutic research for glioma therapy

Abstract

Gliomas are primary malignancies of the brain. Tumors are staged based on malignancy, nuclear atypia, and infiltration of the surrounding brain parenchyma. Tumors are often diagnosed once patients become symptomatic, at which time the lesion is sizable. Glioblastoma (grade IV glioma) is highly aggressive and difficult to treat. Most tumors are diagnosed de novo. The gold standard of therapy, implemented over a decade ago, consists of fractionated radiotherapy and temozolomide, but unfortunately, chemotherapeutic resistance arises. Recurrence is common after initial therapy. The tumor microenvironment plays a large role in cancer progression and its manipulation can repress progression. The advent and implementation of immunotherapy, via manipulation and activation of cytotoxic T cells, have had an outstanding impact on reducing morbidity and mortality associated with peripheral cancers under certain clinical circumstances. An arsenal of immunotherapeutics is currently under clinical investigation for safety and efficacy in the treatment of newly diagnosed and recurrent high grade gliomas. These immunotherapeutics encompass antibody-drug conjugates, autologous infusions of modified chimeric antigen receptor expressing T cells, peptide vaccines, autologous dendritic cell vaccines, immunostimulatory viruses, oncolytic viruses, checkpoint blockade inhibitors, and drugs which alter the behavior of innate immune cells. Effort is focusing on determining which patient populations will benefit the most from these treatments and why. Research addressing synergism between treatment options is gaining attention. While advances in the treatment of glioma stagnated in the past, we may see a considerable evolution in the management of the disease in the upcoming years.

Glioblastoma Treatments: An Account of Recent Industrial Developments

“…At the same time, there has been a real surge in the number of publications related to this topic (from 15 in 1999 to 164 in 2017 according to pubmed). The reader is redirected toward the large number of excellent reviews on this topic (Calinescu et al, 2015 ; Binder et al, 2016 ; Desaia et al, 2016 ; Hodges et al, 2016 ; Kamran et al, 2016 ; Dunn-Pirio and Vlahovic, 2017 ; Farber et al, 2017 ; Lyon et al, 2017 ; McGranahan et al, 2017 ; Miyauchi and Tsirka, 2017 ; Sahebjam et al, 2017 ; Tivnan et al, 2017 ), providing details about current or past clinical trials (Binder et al, 2016 ), and the different modes of action of these treatments (Calinescu et al, 2015 ; Curry and Lim, 2015 ).…”

Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice

“…Brain tumors are also the leading cause of cancer deaths in children 2 . In adults, primary brain tumors (tumors that originate in the brain) include the most aggressive glioblastoma multiform (GBM) which after optimal therapy nearly always recurs after which most patients do not survive beyond one year 3,4 . More prevalent are brain tumors from other parts of the body (primarily from breast and lung, but also from colon, kidney and melanoma) that metastasize to the brain and account for about 90% of all brain tumors.…”

Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma

“…Whenever possible, the current standard therapy of malignant glioma is surgical resection [3], which could achieve cytoreduction, relieve mass effect and provide adequate tissue for tumor histologic characterization and establishing molecular genotype [29]. Combined radiotherapy, chemotherapy, and chemoradiation therapy is also needed, but it is far from combating the tumor progression [30]. A more comprehensively prognostic classi cation integrating genetic and epigenetic signatures are even more important than clinical factors.…”