A New Hope in Immunotherapy for Malignant Gliomas: Adoptive T Cell Transfer Therapy

Abstract

Immunotherapy emerged as a promising therapeutic approach to highly incurable malignant gliomas due to tumor-specific cytotoxicity, minimal side effect, and a durable antitumor effect by memory T cells. But, antitumor activities of endogenously activated T cells induced by immunotherapy such as vaccination are not sufficient to control tumors because tumor-specific antigens may be self-antigens and tumors have immune evasion mechanisms to avoid immune surveillance system of host. Although recent clinical results from vaccine strategy for malignant gliomas are encouraging, these trials have some limitations, particularly their failure to expand tumor antigen-specific T cells reproducibly and effectively. An alternative strategy to overcome these limitations is adoptive T cell transfer therapy, in which tumor-specific T cells are expanded ex vivo rapidly and then transferred to patients. Moreover, enhanced biologic functions of T cells generated by genetic engineering and modified immunosuppressive microenvironment of host by homeostatic T cell expansion and/or elimination of immunosuppressive cells and molecules can induce more potent antitumor T cell responses and make this strategy hold promise in promoting a patient response for malignant glioma treatment. Here we will review the past and current progresses and discuss a new hope in adoptive T cell therapy for malignant gliomas.

Concise Review: Targeting Cancer Stem Cells Using Immunologic Approaches

“…Major conceptual and technical advances in immunology over the past 25 years have led to a new understanding of cellular and molecular interactions between the immune system and tumor cells. In parallel, recent advances in tumor immunotherapy have provided powerful new therapeutic approaches that have produced durable clinical responses with limited toxicities in a small subset of patients . Although it is currently not known what accounts for these durable remissions receiving immunotherapy, the possibility that this may be related to the ability of these therapies to target CSCs warrants further exploration.…”

Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors

“…GBM-specific tumor antigens (Ag) recognized by ab T cells, 10 stress-induced molecules activating gd T cells or specific surface molecules that can trigger ADCC have been identified and proposed for effective immunotherapies in GBM. 11 Clinical trials have been performed by systemic or intracranial infusion of ex vivo-amplified T lymphocytes from either the GBM tumor, draining lymph nodes, or HLA-mismatched T cells from healthy donors, 12 but have had limited success. Post-resection administrations of selected GBM-reactive cytotoxic T cells in the vicinity of the primary tumor could represent a unique opportunity to deliver concentrated cellular immunotherapy directly to the site of residual malignancy.…”

Lenalidomide enhances the function of chimeric antigen receptor T cells against the epidermal growth factor receptor variant III by enhancing immune synapses

“…Thus far, a variety of immunotherapeutic approaches including cancer vaccines and antibody-mediated and cell-based therapies have been tested to treat cancers. [3][4][5] However, these therapies have major drawbacks such as major histocompatibility complex restriction, nonspecific killing and technical difficulties for expansion ex vivo. 5 The epidermal growth factor receptor (EGFR) is amplified and overexpressed in 40-60% of GBM.…”

“…[3][4][5] However, these therapies have major drawbacks such as major histocompatibility complex restriction, nonspecific killing and technical difficulties for expansion ex vivo. 5 The epidermal growth factor receptor (EGFR) is amplified and overexpressed in 40-60% of GBM. [6][7][8] One of the most effective immunotherapeutic antigens is the EGFR variant III (EGFRvIII), with an in-frame deletion of 801 base pairs in the extracellular domain.…”