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      Characterization and Treatment of Spinal Tumors

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          Abstract

          The prevalence of spinal tumors is rare in comparison to brain tumors which encompass most central nervous system tumors. Tumors of the spine can be divided into primary and metastatic tumors with the latter being the most common presentation. Primary tumors are subdivided based on their location on the spinal column and in the spinal cord into intramedullary, intradural extramedullary, and primary bone tumors. Back pain is a common presentation in spine cancer patients; however, other radicular pain may be present. Magnetic resonance imaging (MRI) is the imaging modality of choice for intradural extramedullary and intramedullary tumors. Plain radiographs are used in the initial diagnosis of primary bone tumors while Computed tomography (CT) and MRI may often be necessary for further characterization. Complete surgical resection is the treatment of choice for spinal tumors and may be curative for well circumscribed lesions. However, intralesional resection along with adjuvant radiation and chemotherapy can be indicated for patients that would experience increased morbidity from damage to nearby neurological structures caused by resection with wide margins. Even with the current treatment options, the prognosis for aggressive spinal cancer remains poor. Advances in novel treatments including molecular targeting, immunotherapy and stem cell therapy provide the potential for greater control of malignant and metastatic tumors of the spine.

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          A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

          We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up. All patients demonstrated detectable transient expansion of CART-EGFRvIII cells in peripheral blood. Seven patients had post-CART-EGFRvIII surgical intervention, which allowed for tissue-specific analysis of CART-EGFRvIII trafficking to the tumor, phenotyping of tumor-infiltrating T cells and the tumor microenvironment in situ, and analysis of post-therapy EGFRvIII target antigen expression. Imaging findings after CART immunotherapy were complex to interpret, further reinforcing the need for pathologic sampling in infused patients. We found trafficking of CART-EGFRvIII cells to regions of active GBM, with antigen decrease in five of these seven patients. In situ evaluation of the tumor environment demonstrated increased and robust expression of inhibitory molecules and infiltration by regulatory T cells after CART-EGFRvIII infusion, compared to pre-CART-EGFRvIII infusion tumor specimens. Our initial experience with CAR T cells in recurrent GBM suggests that although intravenous infusion results in on-target activity in the brain, overcoming the adaptive changes in the local tumor microenvironment and addressing the antigen heterogeneity may improve the efficacy of EGFRvIII-directed strategies in GBM.
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            Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial.

            Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma.
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              Molecular targeted therapy: Treating cancer with specificity

              Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression, and metastasis. Many molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers. This review provides an update on the different types of molecular targeted therapies used in the treatment of cancer, focusing on the fundamentals of molecular targeted therapy, its mode of action in cancer treatment, as well as its advantages and limitations.
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                Author and article information

                Journal
                9918470787506676
                51993
                Intensive Care Res
                Intensive Care Res
                Intensive care research
                2666-9862
                28 September 2022
                December 2022
                8 September 2022
                02 February 2023
                : 2
                : 3-4
                : 76-95
                Affiliations
                [1 ]School of Medicine, University of South Florida, Tampa, USA
                [2 ]Department of Neurosurgery, University of Florida, Gainesville, USA
                Author notes

                Authors’ Contribution

                E.A.—Primary manuscript preparation (lead author), manuscript editing. E.P. Primary manuscript preparation (supporting author), manuscript editing, figure preparation. B.L.-W.—Supervision and idea curation, primary manuscript preparation (supporting author), manuscript editing.

                Article
                NIHMS1835073
                10.1007/s44231-022-00014-3
                9893847
                36741203
                c0c43137-7041-4b08-a0f7-06f37ab4412d

                This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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                spinal tumors,management,updated care,critical care
                spinal tumors, management, updated care, critical care

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