Dendritic cell immunotherapy for brain tumors

Antonios, Joseph; Everson, Richard; Liau, Linda M.

doi:10.1007/s11060-015-1830-1

Cited by 11 publications

(5 citation statements)

References 47 publications

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“…Due to the successes of immunotherapies in other cancer types (5), combined with the realization that the CNS is not an hermetically immunoprivileged site (6), enthusiasm is growing regarding the use of immune-based treatments for patients with glioblastoma. Indeed, vaccine approaches targeting EGFRvIII (7) and other shared epitopes (8), autologous dendritic cell (9) and heat shock protein (10) vaccines, and other modalities including the checkpoint blockade agents are in clinical trials for glioblastoma. However, our understanding of how these immune-based strategies, designed to enhance tumor-specific T cell recognition and effector function, control glioblastoma progression has been limited by our ability to identify and monitor tumor-specific T cell responses.…”

Section: Introductionmentioning

confidence: 99%

Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach

Johanns

Ward

Miller

et al. 2016

Cancer Immunology Research

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The “cancer immunogenomics” paradigm has facilitated the search for tumor-specific antigens over the last 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific “neoantigens” in the C57BL/6-derived GL261 and VM/Dk-derived SMA-560 tumor models. Following DNA whole exome and RNA sequencing, high-affinity candidate neoepitopes were predicted and screened for immunogenicity by ELISPOT and tetramer analyses. GL261 and SMA-560 harbored 4,932 and 2,171 non-synonymous exome mutations, respectively, of which less than half were expressed. To establish the immunogenicities of H-2Kb and H-2Db candidate neoantigens, we assessed the ability of the epitopes predicted in silico to be the highest affinity binders to activate tumor-infiltrating T cells harvested from GL261 and SMA-560 tumors. Using IFNγ ELISPOT, we confirmed H-2Db–restricted Imp3D81N (GL261) and Odc1Q129L (SMA-560) along with H-2Kb–restricted E2f8K272R (SMA-560) as endogenous tumor-specific neoantigens that are functionally immunogenic. Furthermore, neoantigen-specific T cells to Imp3D81N and Odc1Q129L were detected within intracranial tumors as well as cervical draining lymph nodes by tetramer analysis. By establishing the immunogenicities of predicted high-affinity neoepitopes in these models, we extend the immunogenomics-based neoantigen discovery pipeline to glioblastoma models and provide a tractable system to further study the mechanism of action of T cell–activating immunotherapeutic approaches in preclinical models of glioblastoma.

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Section: Introductionmentioning

confidence: 99%

Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach

Johanns

Ward

Miller

et al. 2016

Cancer Immunology Research

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“…For the neoantigen found in individual melanoma, a firm immune response was established [ 38 ]. In addition, glioblastoma DC therapy where the DC is loaded with cancer stem cell lysate shows remarkable results without affecting the bone marrow [ 39 , 40 , 41 , 42 ]. The first results of an autologous DC vaccine in a phase 3 clinical trial were recently reported [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

The Dilemma of Cure and Damage in Oligodendroglioma: Ways to Tip the Balance Away from the Damage

Torensma

2018

Cancers

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Current treatments for oligodendrogliomas are powerful but have a negative impact on the rest of the body. The bone marrow is damaged by the chemotherapeutics, but other parts of the body are also affected. In this paper, the current treatment method and its collateral damage is described. Therefore, therapies are needed that are more effective against the tumor while having less negative effects on the patient’s quality of life. Some potential therapies include optimal removal of the tumor by fluorescent-guided surgery (FGS), intraoperative desorption electrospray ionization-mass spectrometry (DESI-MS), better monitoring of the effects of therapy by pseudo-coloring shades of gray of MRI pictures, and using recent data from RNA sequencing of single cells and immunotherapy. These are all open new ways of treating this tumor. The RNA sequencing of single tumor cells unravels specific tumor antigens present in the differentiation status of the cancer cell. Stem cell antigens were expressed in dividing cells, while hypoxia inducible factor-α (HIF-1α) is expressed in all tumor cells. Cancer stem cell antigens can be loaded on dendritic cells to induce cytotoxic T-cells directed to cancer stem cells. These recent discoveries suggest a better quality of life with the same overall survival.

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“…DCs can also facilitate the killing of tumor cells without affecting normal cells. Therefore, DC-based immunotherapy has been proposed as a promising cancer treatment method in various types of malignancies, including brain tumors (102)(103)(104).…”

Section: Dendritic Cell (Dc) Immunotherapy Dcs Are Professionalmentioning

confidence: 99%

Development of immunotherapy for brain metastasis (Review)

et al. 2020

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Brain metastasis (BM) is associated with a poor prognosis, with the typical overall survival rate ranging from weeks to months in the absence of treatment. Although the concept of immune privilege in the central nervous system has eroded over time, the advent of immunotherapy has opened a new set of potential therapeutic options for patients with BM. Recently, immunotherapy has been demonstrated to confer survival advantages to patients with multiple malignancies commonly associated with BMs. Data from a number of clinical trials have demonstrated that immune checkpoint inhibitors are effective for patients with BM. In addition, cellular therapies, including the application of chimeric antigen receptors T-cell therapy and dendritic cell vaccine, have also been utilized in the treatment of BM. In the present review, preclinical and clinical evidence supporting the applicability of immunotherapy for the treatment of BMs from melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were examined, where the challenges and safety of this treatment modality were also discussed. Contents 1. Introduction 2. Biology of brain metastases 3. Evidence of treatment with ICIs for patients with BMs 4. Cellular therapy for patients with BMs 5. Conclusions

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Dendritic cell immunotherapy for brain tumors

Cited by 11 publications

References 47 publications

Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach

Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach

The Dilemma of Cure and Damage in Oligodendroglioma: Ways to Tip the Balance Away from the Damage

Development of immunotherapy for brain metastasis (Review)

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