Passive Immunotherapeutic Strategies for the Treatment of Malignant Gliomas

Nagasawa, Daniel T.; Fong, Christina; Yew, Andrew; Spasić, Marko; Garcia, Heather M.; Kruse, Carol A.; Yang, Isaac

doi:10.1016/j.nec.2012.04.008

Cited by 15 publications

(9 citation statements)

References 115 publications

(157 reference statements)

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“…Active immunotherapy entails the arming of immune system to initiate long-term memory by allowing the immune system to fight tumor cells long after the administration of the therapy [ 85 , 86 ]. Passive immunotherapy on the other hand, is the administration of immunotherapeutic agents that are based on the elements of the immune system, temporary, but still could instill a long term memory under certain conditions [ 87 ]. Adoptive immunotherapy or adoptive cell transfer (ACT) involves the isolation of T-cells from patients.…”

Section: Interleukin 13 Receptor Alpha 2 (Il-13ra2) In Glioma Treamentioning

confidence: 99%

Receptor-Targeted Glial Brain Tumor Therapies

Sharma

Debinski

2018

IJMS

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Among primary brain tumors, malignant gliomas are notably difficult to manage. The higher-grade tumors represent an unmet need in medicine. There have been extensive efforts to implement receptor-targeted therapeutic approaches directed against gliomas. These approaches include immunotherapies, such as vaccines, adoptive immunotherapy, and passive immunotherapy. Targeted cytotoxic radio energy and pro-drug activation have been designed specifically for brain tumors. The field of targeting through receptors progressed significantly with the discovery of an interleukin 13 receptor alpha 2 (IL-13RA2) as a tumor-associated receptor over-expressed in most patients with glioblastoma (GBM) but not in normal brain. IL-13RA2 has been exploited in novel experimental therapies with very encouraging clinical responses. Other receptors are specifically over-expressed in many patients with GBM, such as EphA2 and EphA3 receptors, among others. These findings are important in view of the heterogeneity of GBM tumors and multiple tumor compartments responsible for tumor progression and resistance to therapies. The combined targeting of multiple receptors in different tumor compartments should be a preferred way to design novel receptor-targeted therapeutic approaches in gliomas.

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Section: Interleukin 13 Receptor Alpha 2 (Il-13ra2) In Glioma Treamentioning

confidence: 99%

Receptor-Targeted Glial Brain Tumor Therapies

Sharma

Debinski

2018

IJMS

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“…Adoptive immunotherapy is the extraction and ex-vivo activation of native immune cells of patients followed by intravenous injection into human body to target infections [56]. It is an effective and efficient technique to build up immunity against viruses.…”

Section: Adoptive Immunotherapymentioning

confidence: 99%

Immunotherapeutic strategies for sexually transmitted viral infections: HIV, HSV and HPV

Wahid

Ali

Idrees

et al. 2016

Cellular Immunology

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More than 1 million sexually transmitted infections (STIs) are acquired each day globally. Etiotropic drugs cannot effectively control infectious diseases therefore, there is a dire need to explore alternative strategies especially those based on the regulation of immune system. The review discusses all rational approaches to develop better understanding towards immunotherapeutic strategies based on modulation of immune system in an attempt to curb the elevating risk of infectious diseases such as HIV, HPV and HSV because of their high prevalence. Development of monoclonal antibodies, vaccines and several other immune based treatments are promising alternative strategies that are offering new opportunities to eradicate pathogens.

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“…The DNA damage results in calcium-dependent apoptosis and autophagy, eventually leading to cell death. TMZ is also reported to activate p53 and p21 WAF1/Cip1 -mediated G2/M cell cycle arrest with subsequent apoptosis or senescence (Nagasawa et al, 2012). Although TMZ is well-tolerated and has an overall beneficial impact on patient survival, it has also been well-described to induce immunosuppression, most often described as various forms of lymphopenia (Lanzetta et al, 2003; Kocher et al, 2005).…”

Section: Therapeutic Targeting Of Tregsmentioning

confidence: 99%

Targeting Tregs in Malignant Brain Cancer: Overcoming IDO

Wainwright¹,

Dey²,

Chang³

et al. 2013

Front. Immunol.

109

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One of the hallmark features of glioblastoma multiforme (GBM), the most common adult primary brain tumor with a very dismal prognosis, is the accumulation of CD4+CD25+Foxp3+ regulatory T cells (Tregs). Regulatory T cells (Tregs) segregate into two primary categories: thymus-derived natural Tregs (nTregs) that develop from the interaction between immature T cells and thymic epithelial stromal cells, and inducible Tregs (iTregs) that arise from the conversion of CD4+FoxP3− T cells into FoxP3 expressing cells. Normally, these Treg subsets complement one another’s actions by maintaining tolerance of self-antigens, thereby suppressing autoimmunity, while also enabling effective immune responses toward non-self-antigens, thus promoting infectious protection. However, Tregs have also been shown to be associated with the promotion of pathological outcomes, including cancer. In the setting of GBM, nTregs appear to be primary players that contribute to immunotherapeutic failure, ultimately leading to tumor progression. Several attempts have been made to therapeutically target these cells with variable levels of success. The blood brain barrier-crossing chemotherapeutics, temozolomide, and cyclophosphamide (CTX), vaccination against the Treg transcriptional regulator, FoxP3, as well as mAbs against Treg-associated cell surface molecules CD25, CTLA-4, and GITR are all different therapeutic approaches under investigation. Contributing to the poor success of past approaches is the expression of indoleamine 2,3-dioxygenase 1 (IDO), a tryptophan catabolizing enzyme overexpressed in GBM, and critically involved in regulating tumor-infiltrating Treg levels. Herein, we review the current literature on Tregs in brain cancer, providing a detailed phenotype, causative mechanisms involved in their pathogenesis, and strategies that have been used to target this population, therapeutically.

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Passive Immunotherapeutic Strategies for the Treatment of Malignant Gliomas

Cited by 15 publications

References 115 publications

Receptor-Targeted Glial Brain Tumor Therapies

Receptor-Targeted Glial Brain Tumor Therapies

Immunotherapeutic strategies for sexually transmitted viral infections: HIV, HSV and HPV

Targeting Tregs in Malignant Brain Cancer: Overcoming IDO

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