About this Research Topic
Malignant tumors of the central nervous system (CNS) remain one of the most fatal of all cancers in children and adults. The infiltrative nature of brain and spinal cord cancers along with their intricate anatomical location does not lend itself well to current standard of care (which include gross total surgical resection where feasible, followed by radiation with or without chemotherapy). As a result, a large percentage of CNS tumors are either refractory to therapy or recur in the majority of the treated patients. Cell-based immunotherapy is a transformative and potentially curative approach with minimal long-term adverse effects on health. T cell therapies have run the entire spectrum: from ex vivo expanded tumor infiltrating lymphocytes, to genetically modified T cells expressing transgenic T cell receptors (TCRs), to chimeric antigen receptors (CARs) that target tumor-associated antigens. Although no cell-based therapy for CNS tumors has received regulatory approval, early phase clinical trials in advanced glioblastoma have indicated clinical benefit in some patients who have failed other forms of salvage therapy.
Improved understanding of the functional complexity of T cells and the presence of shared targets has recently enabled the consolidation of CNS tumors under the same therapeutic investigation, independent of the histopathological diagnosis. This has led to new clinical trials where CAR T cells targeting epidermal growth factor receptor variant III (EGFRvIII), human epidermal growth factor receptor 2 (HER2), and interleukin-13 receptor alpha 2 (IL13Rα2) as well as tumor antigen associated T lymphocytes targeting Wilm's tumor gene product 1 (WT1), preferentially expressed antigen in melanoma (PRAME) and survivin, were used to target grade II or III gliomas, ependymoma, medulloblastoma, atypical teratoid/rhabdoid tumor, diffuse intrinsic pontine gliomas among others, apart from glioblastoma.
Additionally, investigational approaches to overcome the limitations of T cell trafficking to the tumor site, immune inhibition, and poor T cell persistence have provided encouraging results in basic and preclinical models. This Research Topic will be collating the state of the science in treating CNS tumors with T cells as well as expert opinion on integrating these approaches to clinical practices.
We welcome Original Research articles, Reviews, and expert Opinions along the following themes:
1. Basic, preclinical and clinical research advances in T cell therapy for CNS tumors
2. Novel CNS targets for cell-based therapeutic approaches
3. Enhancing T cell therapy for CNS tumors in combination with approved therapeutic approaches and other experimental therapeutic approaches
4. Improved animal models for understanding T cell function in CNS tumors
5. Loco-regional administration of T cells for CNS tumors - basic and clinical insights
6. Integrating CAR, TCR and antigen-specific T cell approaches to enhance therapeutic efficacy
7. Adaptive clinical trial designs for T cell therapy in CNS tumors
8. Regulatory and logistical considerations in developing T cell therapies for CNS tumors
9. T cells targeting brain metastases
10. Integrating T cell therapy to existing standard of care practices
Keywords: Cell-based immunotherapy, CAR T cells, TCR-Transgenic T cells, antigen-specific T cells, CNS tumors
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