Cellular immunotherapy for malignant gliomas

Abstract

Introduction Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy. Areas covered Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, γδ T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells. Expert opinion While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy.

Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas

“…9,10). We have demonstrated that tumor-specific type 1 CD8 + T cells, which predominantly secrete IFN-γ, but not type 2 CD8 + T cells, can efficiently traffic into brain tumor sites and mediate effective tumor cell killing (11) via the type 1 chemokine CXCL10 (11)(12)(13)(14).…”

Cell transfer‐based immunotherapies in cancer: A review

“…When comparing the TIL effectiveness in different cancers including malignant gliomas, the use of TILs against melanoma is of highest efficiency; however, 50% of melanomas do not reproduce antitumor TILs . This might be a result of the level of accessibility to eligible TILs which is largely dependent upon the tumor characteristics including its size, location, and immunogenicity . An important factor in making a lymphocyte suitable for ACT is its telomere length which is correlated with the persistence of T cells and clinical response after ACT .…”

“…Moreover, ACT with TILs is time-consuming and expensive. 48 When comparing the TIL effectiveness in different cancers including malignant gliomas, 49 the use of TILs against melanoma is of highest efficiency; however, 50% of melanomas do not reproduce antitumor TILs. 38,[50][51][52] This might be a result of the level of accessibility to eligible TILs which is largely dependent upon the tumor characteristics including its size, location, and immunogenicity.…”

“…38,[50][51][52] This might be a result of the level of accessibility to eligible TILs which is largely dependent upon the tumor characteristics including its size, location, and immunogenicity. 49 An important factor in making a lymphocyte suitable for ACT is its telomere length which is correlated with the persistence of T cells and clinical response after ACT. 41 It has been shown that IL-15 and IL-7 are more effective than IL-2 in the proliferation prevention of Tregs.…”

Advances in Cancer Immunotherapy in Solid Tumors

“…CARs can auto signal leading to persistent activation causing potentially lethal cytokine release syndrome in addition to immunologic exhaustion. While the vast majority of ACT technology have focused on T cells, there is interest in expanding this to a variety of MHC unrestricted immune cells including NK cells, cytokine induced killer (CIK) cells and lymphokine activated killer cells (LAK) [95,96,97,98]. …”