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.

KEYWORDS:

• Glioma
• cellular immunotherapy
• dendritic cell vaccine
• adoptive cell transfer
• CAR-T cell therapy

Article highlights

• Cellular immunotherapeutics could be classified into vaccine approaches and adoptive transfer of effector cell approaches.

• Cellular vaccine approaches utilize tumor cells and/or antigen presenting cells, such as dendritic cells.

• Adoptive cell transfer (ACT) approaches can utilize a variety of effector cell types, 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.

• The ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the areas including feasibility in producing cellular therapeutics as well as strategies to promote effector T-cell trafficking to the tumor site and to overcome local and systemic immune suppression.

• With advances of technologies allowing antigen-specific targeting of ACTs, it is critical to expand the list of glioma-speicific antigens that can be safely targeted in future immunotherapies.

This box summarizes key points contained in the article.

Declaration of interest

H Okada is an inventor in the U.S. Patent Application No. 60,611, 797 (Utility Patent Application) ‘Identification of an IL-13 Receptor Alpha2 Peptide Analogue Capable of Enhancing Stimulation of Glioma-Specific CTL Response’. An exclusive licensing agreement has been completed on this application between University of Pittsburgh and Stemline, Inc. In this manuscript, the authors discussed a publication using this peptide, but the data interpretation was done by the entire study team and not by Dr Okada himself. Due to the potential conflicts of interest, Hideho Okada did not solely interpret any data in the current manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work is supported by NIH/NINDS grant R21NS083171 through H Okada.