Iris Mildenberger1, Lukas Bunse, Katharina Ochs, Michael Platten. 1. aDepartment of Neurology, University Hospital Mannheim, Heidelberg University bCCU Neuroimmunology and Brain Tumor Immunology, First Division, German Cancer Research Center (DKFZ) cDepartment of Neurology and National Center for Tumor Diseases, Heidelberg University, Heidelberg, Germany.
Abstract
PURPOSE OF REVIEW: Also owing to the limited efficacy of targeted therapies, there has been a renewed interest in targeting gliomas with immunotherapy. But despite considerable efforts using sophisticated approaches, proof of efficacy beyond case studies is still lacking. The purpose of this review is to summarize and discuss current immunotherapeutic approaches and efforts to understand mechanisms of response and resistance. RECENT FINDINGS: The recent failure of large randomized clinical trials using targeted vaccines and checkpoint inhibitors to improve clinical outcome have underlined the grand challenges in this therapeutic arena and illustrated the necessity to understand the biology of immunotherapeutic interventions before conducting large randomized studies. However, these failures should not distract us from continuing to optimize immunotherapeutic concepts. The recent developments in transgenic T cell technologies and personalized vaccines but also rational combinatorial approaches offer tremendous opportunities and should be exploited carefully in early scientifically driven clinical trials. SUMMARY: A profound understanding of the cellular and molecular mechanisms of response and resistance to immunotherapy to be gained from these thoroughly designed clinical trials will be essential to carve out successful strategies in selected patient populations.
PURPOSE OF REVIEW: Also owing to the limited efficacy of targeted therapies, there has been a renewed interest in targeting gliomas with immunotherapy. But despite considerable efforts using sophisticated approaches, proof of efficacy beyond case studies is still lacking. The purpose of this review is to summarize and discuss current immunotherapeutic approaches and efforts to understand mechanisms of response and resistance. RECENT FINDINGS: The recent failure of large randomized clinical trials using targeted vaccines and checkpoint inhibitors to improve clinical outcome have underlined the grand challenges in this therapeutic arena and illustrated the necessity to understand the biology of immunotherapeutic interventions before conducting large randomized studies. However, these failures should not distract us from continuing to optimize immunotherapeutic concepts. The recent developments in transgenic T cell technologies and personalized vaccines but also rational combinatorial approaches offer tremendous opportunities and should be exploited carefully in early scientifically driven clinical trials. SUMMARY: A profound understanding of the cellular and molecular mechanisms of response and resistance to immunotherapy to be gained from these thoroughly designed clinical trials will be essential to carve out successful strategies in selected patient populations.
Authors: Takumi Kudo; Mirja T Prentzell; Soumya R Mohapatra; Felix Sahm; Zhongliang Zhao; Ingrid Grummt; Wolfgang Wick; Christiane A Opitz; Michael Platten; Edward W Green Journal: Front Immunol Date: 2020-05-14 Impact factor: 7.561
Authors: Sabbir Khan; Sandeep Mittal; Kain McGee; Kristin D Alfaro-Munoz; Nazanin Majd; Veerakumar Balasubramaniyan; John F de Groot Journal: Int J Mol Sci Date: 2020-03-13 Impact factor: 5.923