Clinical implication of cellular vaccine in glioma: current advances and future prospects
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(2020) 39:257
REVIEW
Open Access
Clinical implication of cellular vaccine in glioma: current advances and future prospects Yuanliang Yan1,2, Shuangshuang Zeng1,2, Zhicheng Gong1,2 and Zhijie Xu3*
Abstract Gliomas, especially glioblastomas, represent one of the most aggressive and difficult-to-treat human brain tumors. In the last few decades, clinical immunotherapy has been developed and has provided exceptional achievements in checkpoint inhibitors and vaccines for cancer treatment. Immunization with cellular vaccines has the advantage of containing specific antigens and acceptable safety to potentially improve cancer therapy. Based on T cells, dendritic cells (DC), tumor cells and natural killer cells, the safety and feasibility of cellular vaccines have been validated in clinical trials for glioma treatment. For TAA engineered T cells, therapy mainly uses chimeric antigen receptors (IL13Rα2, EGFRvIII and HER2) and DNA methylation-induced technology (CT antigen) to activate the immune response. Autologous dendritic cells/tumor antigen vaccine (ADCTA) pulsed with tumor lysate and peptides elicit antigen-specific and cytotoxic T cell responses in patients with malignant gliomas, while its prosurvival effect is biased. Vaccinations using autologous tumor cells modified with TAAs or fusion with fibroblast cells are characterized by both effective humoral and cell-mediated immunity. Even though few therapeutic effects have been observed, most of this therapy showed safety and feasibility, asking for larger cohort studies and better guidelines to optimize cellular vaccine efficiency in anti-glioma therapy. Keywords: glioma, cellular vaccine, CART, DC vaccine, tumor lysate vaccine, immunotherapy
Background Arising from supporting glial cells, gliomas represent over 36% of malignant primary central nervous system (CNS) tumors [1]. Gliomas vary in aggressiveness from low-grade to highly malignant, with 5 year overall survival no greater than 35% [2]. According to the pathological features and clinical outcomes, the World Health Organization (WHO) grades gliomas on a scale of I to IV. The most benign brain tumor is designated grade I, has distinct boundaries, grows slowly, rarely spreads and typically arises in childhood. The most common glioma in adults is glioblastoma (GBM), an astrocytoma * Correspondence: [email protected] 3 Department of Pathology, Xiangya Hospital, Central South University, 87 Xiangya Road, Hunan 410008 Changsha, China Full list of author information is available at the end of the article
designated by the WHO as grade IV. GBMs remain among the most difficult brain tumors to treat, with a median survival of less than 2 years, despite surgical resection, radiation, and chemotherapy [3]. Over the past decades, an explosion in the understanding of treatment strategies of gliomas has progressed beyond the standard of care and consists of complete resection followed by radiotherapy and pharmacological treatment with chemotherapeutic agents, such as temozolomide. For example, on the basis of muta
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