The following articles have been recommended for further reading in the field of cancer immunotherapy by JITC’s Editor-in-Chief, Dr. Pedro J. Romero.
“Synthetic DNA-Encoded Monoclonal Antibody Delivery of Anti–CTLA-4 Antibodies Induces Tumor Shrinkage in Vivo,” by Elizabeth K. Duperret et al. Cancer Res 2018 Nov 15;78(22):6363-6370
Despite the clinical success of checkpoint immunotherapies, the complexity of manufacturing mAbs and the high doses at which they are required in patients necessitates approaches offering less frequent delivery and more simple formulations. In the present study, Duperret et al. presents a novel platform validated for the administration of immune checkpoint blockade, including the design and development of DNA-encoded mAbs (DNAb) expressing antibodies targeting CTLA-4 directly through gene delivery technologies. Providing a potentially novel approach to checkpoint therapy, application of optimized DMAbs may allow for more widely available options in the management and treatment of cancer.
“Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma,” by Veronica Huber et al. J Clin Invest 2018 Dec 3;128(12):5505-5516
Resistance to immune checkpoint inhibitor (ICI) therapy is a major barrier experienced by many cancer patients, however, preclinical data has demonstrated that tumor resistance to PD-1 or CTLA-4 blockade can be reverted by myeloid cell depletion. Huber et al. identified a panel of circulating microRNAs (miRs) associated with monocytic myeloid-derived suppressor cell (M-MDSC) activity in melanoma patients, demonstrating a potential tool to assess the role of these cells in ICI resistance. This study highlights a novel strategy to overcome immunotherapy resistance through correcting myeloid dysfunctions in melanoma patients and discusses the potential for using MDSC-miRs as peripheral blood–based biomarkers to monitor systemic immunosuppression in cancer patients.
“Actively personalized vaccination trial for newly diagnosed glioblastoma,” by Norbert Hilf et al. Nature 2019 Jan;565(7738):240-245
Although glioblastomas have limited intratumoral infiltration of immune cells and few mutations, a known hindrance for antigen-unspecific immunotherapies, T cell responses to glioblastomas with a hypermutation phenotype or overrepresented antigens suggest susceptibility to immunotherapy. Hilf et al. reports on the phase I trial of the Glioma Actively Personalized Vaccine Consortium (GAPVAC-101). This study is investigating the integration of highly individualized vaccinations with both unmutated antigens and neoepitopes into standard care to potentially optimize the full range of tumor antigens targeted in patients with newly diagnosed glioblastoma.
“Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma,” by Moshe Sade-Feldman et al. Cell 2018 Nov 1;175(4):998-1013.e20
There is a lack of understanding as to why some patients with metastatic melanoma experience durable responses to checkpoint therapy while most patients are either initially refractory to treatment or acquire resistance over time. To better understand the driving mechanisms behind tumor immune resistance, Sade-Feldman at al. applied high-dimensional single-cell RNA sequencing (scRNAseq) to investigate immune cell transcriptomes from tumor biopsies of patients treated with checkpoint therapy. The presented analysis focuses on unique cells types, CD8+ T cell states and markers found to be predictive of regression or progression of individual tumors in response to checkpoint blockade.
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