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  1. Article ; Online: Glioblastoma vaccines

    Zujian Xiong / Itay Raphael / Michael Olin / Hideho Okada / Xuejun Li / Gary Kohanbash

    EBioMedicine, Vol 100, Iss , Pp 104963- (2024)

    past, present, and opportunities

    2024  

    Abstract: Summary: Glioblastoma (GBM) is one of the most lethal central nervous systems (CNS) tumours in adults. As supplements to standard of care (SOC), various immunotherapies improve the therapeutic effect in other cancers. Among them, tumour vaccines can ... ...

    Abstract Summary: Glioblastoma (GBM) is one of the most lethal central nervous systems (CNS) tumours in adults. As supplements to standard of care (SOC), various immunotherapies improve the therapeutic effect in other cancers. Among them, tumour vaccines can serve as complementary monotherapy or boost the clinical efficacy with other immunotherapies, such as immune checkpoint blockade (ICB) and chimeric antigen receptor T cells (CAR-T) therapy. Previous studies in GBM therapeutic vaccines have suggested that few neoantigens could be targeted in GBM due to low mutation burden, and single-peptide therapeutic vaccination had limited efficacy in tumour control as monotherapy. Combining diverse antigens, including neoantigens, tumour-associated antigens (TAAs), and pathogen-derived antigens, and optimizing vaccine design or vaccination strategy may help with clinical efficacy improvement. In this review, we discussed current GBM therapeutic vaccine platforms, evaluated and potential antigenic targets, current challenges, and perspective opportunities for efficacy improvement.
    Keywords Glioblastoma ; Vaccine platform ; Tumour antigen ; Vaccine efficacy ; Vaccine perspective ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2024-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Quantitative Sodium ( 23 Na) MRI in Pediatric Gliomas

    Aashim Bhatia / Vincent Kyu Lee / Yongxian Qian / Michael J. Paldino / Rafael Ceschin / Jasmine Hect / James M. Mountz / Dandan Sun / Gary Kohanbash / Ian F. Pollack / Regina I. Jakacki / Fernando Boada / Ashok Panigrahy

    Diagnostics, Vol 12, Iss 1223, p

    Initial Experience

    2022  Volume 1223

    Abstract: Background: 23 Na MRI correlates with tumor proliferation, and studies in pediatric patients are lacking. The purpose of the study: (1) to compare total sodium concentration (TSC) between pediatric glioma and non-neoplastic brain tissue using 23 Na MRI; ( ...

    Abstract Background: 23 Na MRI correlates with tumor proliferation, and studies in pediatric patients are lacking. The purpose of the study: (1) to compare total sodium concentration (TSC) between pediatric glioma and non-neoplastic brain tissue using 23 Na MRI; (2) compare tissue conspicuity of bound sodium concentration (BSC) using 23 Na MRI dual echo relative to TSC imaging. Methods: TSC was measured in: (1) non-neoplastic brain tissues and (2) three types of manually segmented gliomas (diffuse intrinsic brainstem glioma (DIPG), recurrent supratentorial low-grade glioma (LGG), and high-grade glioma (HGG)). In a subset of patients, serial changes in both TSC and BSC (dual echo 23 Na MRI) were assessed. Results: Twenty-six pediatric patients with gliomas (median age of 12.0 years, range 4.9–23.3 years) were scanned with 23 Na MRI. DIPG treated with RT demonstrated higher TSC values than the uninvolved infratentorial tissues ( p < 0.001). Recurrent supratentorial LGG and HGG exhibited higher TSC values than the uninvolved white matter (WM) and gray matter (GM) ( p < 0.002 for LGG, and p < 0.02 for HGG). The dual echo 23 Na MRI suppressed the sodium signal within both CSF and necrotic foci. Conclusion: Quantitative 23 Na MRI of pediatric gliomas demonstrates a range of values that are higher than non-neoplastic tissues. Dual echo 23 Na MRI of BCS improves tissue conspicuity relative to TSC imaging.
    Keywords sodium ; MRI ; brain tumor ; Medicine (General) ; R5-920
    Subject code 333 ; 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma

    Alexandra Foster / Shubhanchi Nigam / David S Tatum / Itay Raphael / Jide Xu / Rajeev Kumar / Elizabeth Plakseychuk / Joseph D Latoche / Sarah Vincze / Bo Li / Rajan Giri / Lauren H McCarl / Robert Edinger / Murat Ak / Vishal Peddagangireddy / Lesley M Foley / T Kevin Hitchens / Rivka R Colen / Ian F Pollack /
    Ashok Panigrahy / Darren Magda / Carolyn J Anderson / W Barry Edwards / Gary Kohanbash

    EBioMedicine, Vol 71, Iss , Pp 103571- (2021)

    2021  

    Abstract: Background: Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising therapeutic strategy for treating gliomas, a significant barrier is the CD11b+ tumour-associated myeloid cells (TAMCs), a ... ...

    Abstract Background: Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising therapeutic strategy for treating gliomas, a significant barrier is the CD11b+ tumour-associated myeloid cells (TAMCs), a heterogeneous glioma infiltrate comprising up to 40% of a glioma's cellular mass that inhibits anti-tumour T-cell function and promotes tumour progression. A theranostic approach uses a single molecule for targeted radiopharmaceutical therapy (TRT) and diagnostic imaging; however, there are few reports of theranostics targeting the tumour microenvironment. Methods: Utilizing a newly developed bifunctional chelator, Lumi804, an anti-CD11b antibody (αCD11b) was readily labelled with either Zr-89 or Lu-177, yielding functional radiolabelled conjugates for PET, SPECT, and TRT. Findings: 89Zr/177Lu-labeled Lumi804-αCD11b enabled non-invasive imaging of TAMCs in murine gliomas. Additionally, 177Lu-Lumi804-αCD11b treatment reduced TAMC populations in the spleen and tumour and improved the efficacy of checkpoint immunotherapy. Interpretation: 89Zr- and 177Lu-labeled Lumi804-αCD11b may be a promising theranostic pair for monitoring and reducing TAMCs in gliomas to improve immunotherapy responses. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
    Keywords Theranostics ; targeted radiotherapy ; immunoPET ; checkpoint immunotherapy ; gliomas ; bifunctional chelator ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment

    Sören Müller / Gary Kohanbash / S. John Liu / Beatriz Alvarado / Diego Carrera / Aparna Bhaduri / Payal B. Watchmaker / Garima Yagnik / Elizabeth Di Lullo / Martina Malatesta / Nduka M. Amankulor / Arnold R. Kriegstein / Daniel A. Lim / Manish Aghi / Hideho Okada / Aaron Diaz

    Genome Biology, Vol 18, Iss 1, Pp 1-

    2017  Volume 14

    Abstract: Abstract Background Tumor-associated macrophages (TAMs) are abundant in gliomas and immunosuppressive TAMs are a barrier to emerging immunotherapies. It is unknown to what extent macrophages derived from peripheral blood adopt the phenotype of brain- ... ...

    Abstract Abstract Background Tumor-associated macrophages (TAMs) are abundant in gliomas and immunosuppressive TAMs are a barrier to emerging immunotherapies. It is unknown to what extent macrophages derived from peripheral blood adopt the phenotype of brain-resident microglia in pre-treatment gliomas. The relative proportions of blood-derived macrophages and microglia have been poorly quantified in clinical samples due to a paucity of markers that distinguish these cell types in malignant tissue. Results We perform single-cell RNA-sequencing of human gliomas and identify phenotypic differences in TAMs of distinct lineages. We isolate TAMs from patient biopsies and compare them with macrophages from non-malignant human tissue, glioma atlases, and murine glioma models. We present a novel signature that distinguishes TAMs by ontogeny in human gliomas. Blood-derived TAMs upregulate immunosuppressive cytokines and show an altered metabolism compared to microglial TAMs. They are also enriched in perivascular and necrotic regions. The gene signature of blood-derived TAMs, but not microglial TAMs, correlates with significantly inferior survival in low-grade glioma. Surprisingly, TAMs frequently co-express canonical pro-inflammatory (M1) and alternatively activated (M2) genes in individual cells. Conclusions We conclude that blood-derived TAMs significantly infiltrate pre-treatment gliomas, to a degree that varies by glioma subtype and tumor compartment. Blood-derived TAMs do not universally conform to the phenotype of microglia, but preferentially express immunosuppressive cytokines and show an altered metabolism. Our results argue against status quo therapeutic strategies that target TAMs indiscriminately and in favor of strategies that specifically target immunosuppressive blood-derived TAMs.
    Keywords Glioma ; Single-cell sequencing ; Immunotherapy ; Macrophage ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Subject code 610
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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