Faculty Opinions recommendation of IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression.

2015 ◽  
Author(s):  
Xiaojing Ma
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Tumor Antigen ◽  
Antigen Expression ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Macrophage Response ◽  
Engineered T Cells ◽  
Tumor Antigen Expression

scholarly journals Functional Comparison of Engineered T Cells Carrying a Native TCR versus TCR-like Antibody–Based Chimeric Antigen Receptors Indicates Affinity/Avidity Thresholds

2014 ◽  
Vol 193 (11) ◽  
pp. 5733-5743 ◽  
Author(s):  
Ravit Oren ◽  
Moran Hod-Marco ◽  
Maya Haus-Cohen ◽  
Sharyn Thomas ◽  
Dan Blat ◽  
...  
Keyword(s):  
T Cells ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Engineered T Cells

Characterization of the immune tumor microenvironment of HER2-positive breast cancer following treatment with entinostat and immune checkpoint inhibition.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15061-e15061
Author(s):  
Evanthia T. Roussos Torres ◽  
Dimitrios N Sidiropoulos ◽  
Emily Davis-Marcisak ◽  
Luciane Tsukamoto Kagohara ◽  
Roisin M. Connolly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Tumor Antigen ◽  
Immune Checkpoint ◽  
Tumor Antigens ◽  
Differential Expression Analysis ◽  
Antigen Expression ◽  
Tumor Antigen Expression

e15061 Background: HER2+ breast cancers are known to be less-immunogenic and associated with low response rates to immune checkpoint inhibitors (ICIs). A combination of immunosuppressive signals that prevent cytotoxic T cells from infiltrating the tumor microenvironment (TME) and, low tumor antigen expression, contribute to immunotherapy resistance in this population. Epigenetic modulators can both reexpress tumor antigens and rewire the immunosuppressive environment. We previously used a histone deacetylase inhibitor, entinostat (ENT), in combination with ICIs to reverse the immunosuppressive TME and increase tumor antigen expression in a NeuN HER2+ mouse model of breast cancer. Our results showed that ENT in combination with anti-PD-1, anti-CTLA-4, provided a significant survival benefit compared to either treatment alone. Methods: This current study employs single cell RNA-sequencing on whole tumor samples from mice treated with ICIs and entinostat to investigate the role of epigenetic inhibitors in rewiring the expression of tumor antigens and the cellular landscape of the TME. We generate single cell data over 54,000 cells from 20 tumors treated with entinostat alone or in combination with anti-PD1 and anti-CTLA4 and their combination. Results: Analysis of cells in the TME identifies consistent proportion of monocytes, macrophages, T-cells, Myeloid Derived Suppressor Cells (MDSCs) and Cancer Associated Fibroblasts (CAFs) before and after treatment. Differential expression analysis within the cell types identifies distinct subpopulations and we explore those that are either proportionally higher or lower in each treatment group. Notably, pathway analysis on differentially expressed genes of each cell type identified that combination entinostat and checkpoint treatment increased T cell activation, leukocyte proliferation, myeloid leukocyte and neutrophil migration, and decreased Wnt signaling and histone modifications in tumor cells. These results are being corroborated in patient samples from a parallel clinical trial to provide translational relevance. Conclusions: Our current work provides insights into the transcriptional network within a breast tumor after treatment with ENT+ICIs. We predict our findings will bring us closer to identifying additional therapeutic targets and ultimately improve survival rates of patients with less-immunogenic tumors.

scholarly journals Genetically engineered T cells for cancer immunotherapy

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Dan Li ◽  
Xue Li ◽  
Wei-Lin Zhou ◽  
Yong Huang ◽  
Xiao Liang ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Hematological Malignancies ◽  
Genetically Engineered ◽  
Immune Checkpoints ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Recognition Method ◽  
Engineered T Cells ◽  
Mutant Cells

Abstract T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors (TCRs). Cancer immunotherapy, by relying on this basic recognition method, boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells. T cells genetically equipped with chimeric antigen receptors (CARs) or TCRs have shown remarkable effectiveness in treating some hematological malignancies, although the efficacy of engineered T cells in treating solid tumors is far from satisfactory. In this review, we summarize the development of genetically engineered T cells, outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy, and discuss strategies for improving the performance of these T cells in fighting cancers.

scholarly journals Immunotherapy for Osteosarcoma: Genetic Modification of T cells Overcomes Low Levels of Tumor Antigen Expression

2009 ◽  
Vol 17 (10) ◽  
pp. 1779-1787 ◽  
Author(s):  
Nabil Ahmed ◽  
Vita S Salsman ◽  
Eric Yvon ◽  
Chrystal U Louis ◽  
Laszlo Perlaky ◽  
...  
Keyword(s):  
T Cells ◽  
Genetic Modification ◽  
Tumor Antigen ◽  
Antigen Expression ◽  
Low Levels ◽  
Tumor Antigen Expression

scholarly journals Chimeric Antigen Receptor-Engineered T Cells for Immunotherapy of Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Marc Cartellieri ◽  
Michael Bachmann ◽  
Anja Feldmann ◽  
Claudia Bippes ◽  
Slava Stamova ◽  
...  
Keyword(s):  
T Cells ◽  
First Generation ◽  
Specific Immunotherapy ◽  
Third Generation ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Tumor Patients ◽  
Engineered T Cells ◽  
Clinical Responses ◽  
Immunotherapy Of Cancer

CD4+andCD8+T lymphocytes are powerful components of adaptive immunity, which essentially contribute to the elimination of tumors. Due to their cytotoxic capacity, T cells emerged as attractive candidates for specific immunotherapy of cancer. A promising approach is the genetic modification of T cells with chimeric antigen receptors (CARs). First generation CARs consist of a binding moiety specifically recognizing a tumor cell surface antigen and a lymphocyte activating signaling chain. The CAR-mediated recognition induces cytokine production and tumor-directed cytotoxicity of T cells. Second and third generation CARs include signal sequences from various costimulatory molecules resulting in enhanced T-cell persistence and sustained antitumor reaction. Clinical trials revealed that the adoptive transfer of T cells engineered with first generation CARs represents a feasible concept for the induction of clinical responses in some tumor patients. However, further improvement is required, which may be achieved by second or third generation CAR-engrafted T cells.

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