Low MxA Expression Predicts Better Immunotherapeutic Outcomes in Glioblastoma Patients Receiving Heat Shock Protein Peptide Complex 96 Vaccination

Wang, Yi; Li, Chunzhao; Chi, Xiaohan; Huang, Xijian; Gao, Hua; Ji, Nan; Zhang, Yang

doi:10.3389/fonc.2022.865779

Cited by 5 publications

(2 citation statements)

References 76 publications

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“…HSP peptide complex-96 (HSPPC-96) is the most widely used to treat gliomas [ 787 ]. A trial in rGB patients tested this hypothesis and showed an increase in the mOS, a specific peripheral immune response to the peptides bound to HSPPC-96, a focal cellular infiltrate of CD4+ and CD8+ and, in addition, brain biopsies were consistent with specific immune responses at the tumor site [ 678 , 679 ]. A following phase II trial (NCT01814813) failed to demonstrate a survival benefit for patients treated with HSPPC-96 alone or in combination with BEV compared to BEV alone [ 680 ].…”

Section: Immunotherapiesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

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Section: Immunotherapiesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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“…Although patients with early-stage disease benefited significantly, the intent-to-treat population as a whole did not. The approach continues to be pursued today with better tools of immunization and monitoring ( 101 – 103 ). In the high-throughput DNA-sequencing era (2012 and onward), patients with melanoma ( 104 – 106 ), glioblastoma ( 107 , 108 ), pancreatic cancer ( 109 ), lung cancer ( 110 ), or bladder cancer ( 106 ) have been immunized with long peptides (or RNA encoding such peptides) containing neoepitopes that were predicted to be presented by MHC I.…”

Section: The Complexity: Mechanistic Expectations Versus Realitymentioning

confidence: 99%

Cancer neoepitopes viewed through negative selection and peripheral tolerance: a new path to cancer vaccines

Srivastava

2024

Journal of Clinical Investigation

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A proportion of somatic mutations in tumors create neoepitopes that can prime T cell responses that target the MHC I–neoepitope complexes on tumor cells, mediating tumor control or rejection. Despite the compelling centrality of neoepitopes to cancer immunity, we know remarkably little about what constitutes a neoepitope that can mediate tumor control in vivo and what distinguishes such a neoepitope from the vast majority of similar candidate neoepitopes that are inefficacious in vivo. Studies in mice as well as clinical trials have begun to reveal the unexpected paradoxes in this area. Because cancer neoepitopes straddle that ambiguous ground between self and non-self, some rules that are fundamental to immunology of frankly non-self antigens, such as viral or model antigens, do not appear to apply to neoepitopes. Because neoepitopes are so similar to self-epitopes, with only small changes that render them non-self, immune response to them is regulated at least partially the way immune response to self is regulated. Therefore, neoepitopes are viewed and understood here through the clarifying lens of negative thymic selection. Here, the emergent questions in the biology and clinical applications of neoepitopes are discussed critically and a mechanistic and testable framework that explains the complexity and translational potential of these wonderful antigens is proposed.

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Heat‐Shock Proteins

2022

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Heat-shock proteins (HSPs), or stress proteins, are abundant and highly conserved, present in all organisms and in all cells. Selected HSPs, also known as chaperones, play crucial roles in folding and unfolding of proteins, assembly of multiprotein complexes, transport and sorting of proteins into correct subcellular compartments, cell-cycle control and signaling, and protection of cells against stress and apoptosis. More recently, HSPs have been shown to be key players in immune responses: during antigen presentation as well as crosspriming, they chaperone and transfer antigenic peptides to class I and class II molecules of the major histocompatibility complexes. In addition, extracellular HSPs can stimulate and cause maturation of professional antigen-presenting cells of the immune system, such as macrophages and dendritic cells. They also chaperone several toll-like receptors, which play a central role in innate immune responses. HSPs constitute a large family of proteins that are often classified based on their molecular weight as Hsp10, Hsp40, Hsp60, Hsp70, Hsp90, etc. This unit contains a table that lists common HSPs and summarizes their characteristics including (a) name, (b) subcellular localization, (c) known function, (d) chromosome assignment, (e) brief comments, and (f) references.

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Low MxA Expression Predicts Better Immunotherapeutic Outcomes in Glioblastoma Patients Receiving Heat Shock Protein Peptide Complex 96 Vaccination

Cited by 5 publications

References 76 publications

Glioblastoma Therapy: Past, Present and Future

Glioblastoma Therapy: Past, Present and Future

Cancer neoepitopes viewed through negative selection and peripheral tolerance: a new path to cancer vaccines

Heat‐Shock Proteins

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