Tumor antigen–specific T cells for immune monitoring of dendritic cell–treated glioblastoma patients

Muller, Isabelle S.; Altherr, Dominik; Eyrich, Matthias; Flesch, Brigitte K.; Friedmann, Kim S.; Ketter, Ralf; Oertel, Joachim; Schwarz, Eva C.; Technau, Antje; Urbschat, Steffi; Eichler, Hermann

doi:10.1016/j.jcyt.2016.05.014

Cited by 6 publications

(5 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…glioblastoma | PET | MRI | immunotherapy | checkpoint blockade G lioblastoma (GBM), the most common primary malignancy of the brain, occurs in both the young and the elderly, with swift and devastating outcomes. While advances in immunotherapy are beginning to reach clinical relevance in GBM (1-4), a corresponding improvement in effective monitoring of the immune response is lacking (5)(6)(7). T lymphocytes are the most critical immune cell type for immune surveillance of cancer.…”

mentioning

confidence: 99%

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI

Antonios

Soto

Everson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Contrast-enhanced MRI is typically used to follow treatment response and progression in patients with glioblastoma (GBM). However, differentiating tumor progression from pseudoprogression remains a clinical dilemma largely unmitigated by current advances in imaging techniques. Noninvasive imaging techniques capable of distinguishing these two conditions could play an important role in the clinical management of patients with GBM and other brain malignancies. We hypothesized that PET probes for deoxycytidine kinase (dCK) could be used to differentiate immune inflammatory responses from other sources of contrast-enhancement on MRI. Orthotopic malignant gliomas were established in syngeneic immunocompetent mice and then treated with dendritic cell (DC) vaccination and/or PD-1 mAb blockade. Mice were then imaged with [18F]-FAC PET/CT and MRI with i.v. contrast. The ratio of contrast enhancement on MRI to normalized PET probe uptake, which we term the immunotherapeutic response index, delineated specific regions of immune inflammatory activity. On postmortem examination, FACS-based enumeration of intracranial tumor-infiltrating lymphocytes directly correlated with quantitative [18F]-FAC PET probe uptake. Three patients with GBM undergoing treatment with tumor lysate-pulsed DC vaccination and PD-1 mAb blockade were also imaged before and after therapy using MRI and a clinical PET probe for dCK. Unlike in mice, [18F]-FAC is rapidly catabolized in humans; thus, we used another dCK PET probe, [18F]-clofarabine ([18F]-CFA), that may be more clinically relevant. Enhanced [18F]-CFA PET probe accumulation was identified in tumor and secondary lymphoid organs after immunotherapy. Our findings identify a noninvasive modality capable of imaging the host antitumor immune response against intracranial tumors.

show abstract

mentioning

confidence: 99%

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI

Antonios

Soto

Everson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Immune checkpoint inhibitors that interact with a subset of T cell receptors have resulted in significant clinical effects in almost 10 cancers [ 42 , 43 ], to date, but not in brain tumors. Lastly, advances in immunotherapy treatments that involve peptide vaccines [ 44 ], antigen pulsed dendritic cells [ 45 ], tumor-infiltrating lymphocytes, and chimeric antigen receptor T-cells (CAR T-cells) have shown promise, but their clinical benefits in gliomas remain to be seen [ 46 ]. The U.S. Food and Drug Administration (FDA) recently approved CAR T-cell therapy, which targets cluster of differentiation (CD) 19 + cells in acute lymphoblastic leukemia (ALL) [ 47 ].…”

Section: Targeted Therapies For Gliomasmentioning

confidence: 99%

Receptor-Targeted Glial Brain Tumor Therapies

Sharma

Debinski

2018

IJMS

View full text Add to dashboard Cite

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.

show abstract

“…Further protocols, which expand tumor specific CTLs, may be extended to humans. Tumor antigen-pulsed DCs from HLA-A*02-positive GBM patients can increase CD8 + T cell expansion and specificity ex vivo [ 42 ]. INFγ production is signature to functional CTL effector populations.…”

Section: Discrete Roles Of Immune Cell Populations In Glioma Progressmentioning

confidence: 99%

“…INFγ production is signature to functional CTL effector populations. CTL responses to tumor antigens can be measured by INFγ production as well as effector/target killing ratios, which could help identify potent CTL effector populations for ACT [ 42 ].…”

Section: Discrete Roles Of Immune Cell Populations In Glioma Progressmentioning

confidence: 99%

Contributions of immune cell populations in the maintenance, progression, and therapeutic modalities of glioma

Caponegro

Miyauchi

Tsirka

2018

AIMS Allergy and Immunology

View full text Add to dashboard Cite

Immunotherapies are becoming a promising strategy for malignant disease. Selectively directing host immune responses to target cancerous tissue is a milestone of human health care. The roles of the innate and adaptive immune systems in both cancer progression and elimination are now being realized. Defining the immune cell environment and identifying the contributions of each sub-population of these cells has lead to an understanding of the immunotherapeutic processes, and demonstrated the potential of the immune system to drive cancer shrinkage and sustained immunity against disease. Poorly treated diseases, such as high-grade glioma, suffer from lack of therapeutic efficacy and rapid progression. Immunotherapeutic success in other solid malignancies, such as melanoma, now provides the principals for which this treatment paradigm can be adapted for primary brain cancers. The central nervous system is complex, and relative contributions of immune sub-populations to high grade glioma progression are not fully characterized. Here, we summarize recent research in both animal and humans which add to the knowledge base of how innate and adaptive immune cells contribute to glioma progression, and outline work which has demonstrated their potential to elicit anti-tumorigenic responses. Additionally, we highlight Neuropilin 1, a cell surface receptor protein, describe its signaling functions in the context of immunity, and point to its potential to slow glioma progression.

show abstract

Tumor antigen–specific T cells for immune monitoring of dendritic cell–treated glioblastoma patients

Cited by 6 publications

References 70 publications

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI

Receptor-Targeted Glial Brain Tumor Therapies

Contributions of immune cell populations in the maintenance, progression, and therapeutic modalities of glioma

Contact Info

Product

Resources

About