A5087738037- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune cells in cancer
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Signaling Pathways in Disease
- interferon and immune responses
- Chronic Myeloid Leukemia Treatments
- PARP inhibition in cancer therapy
- Peptidase Inhibition and Analysis
- Phagocytosis and Immune Regulation
- Cancer-related Molecular Pathways
- Hepatocellular Carcinoma Treatment and Prognosis
The University of Texas MD Anderson Cancer Center
2022-2024
The University of Texas Health Science Center at Houston
2022
Abstract Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated 4 (CTLA-4) can provoke T cell–dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features cells require for efficacious ICT remain to be fully elucidated. Herein, we report anti–PD-1 anti–CTLA-4 induce upregulation the transcription factor BHLHE40 tumor antigen–specific CD8+...
The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to eliminate by expanding and/or sustaining T cells with anti-tumor capabilities. However, whether ICT enhance immunity distinct or overlapping mechanisms remains unclear. Here, we compared effective tumor-specific mutant neoantigen (NeoAg) anti-CTLA-4 anti-PD-1 in preclinical models. Both NeoAg induce expansion intratumoral NeoAg-specific CD8 cells, though the degree acquisition effector activity was much more...
Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment the Bcell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both and B-cell lymphoma-extra large (BCLXL) will be successful strategy treat CLL, including for patients who relapse on To test this hypothesis, we conducted pre-clinical investigation LP-118, highly potent moderate BCLXL...
<h3>Background</h3> For cancer immunotherapies such as immune checkpoint therapy (ICT), T cell recognition of tumor antigens is critical for efficacy. Tumor-specific neoantigens (NeoAgs) formed from somatic alterations in cells are largely excluded tolerance and exclusively expressed cells, making them favorable vaccine targets. Significant progress has been made the field NeoAg development, showing promise early-phase clinical trials. Despite this, many fundamental questions about vaccines...
Abstract The goal of cancer vaccines and immune checkpoint therapy (ICT) is to expand sustain T cells with enhanced anti-tumor capabilities. Here, we asked whether these distinct immunotherapies utilize similar cellular functional mechanisms. We used multiple approaches compare effective therapeutic mutant neoantigen (NeoAg) αPD-1, αCTLA-4, or αPD-1 αCTLA-4 ICT in preclinical BrafV600EPten−/−Cdkn2a−/− melanoma models. Synthetic long peptide (SLP) MHC-I NeoAg induced a more than 3-fold...
Supplementary Figure from BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy
The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to eliminate by expanding and/or sustaining T cells with anti-tumor capabilities. However, whether ICT enhance immunity distinct or overlapping mechanisms remains unclear. Here, we compared effective tumor-specific mutant neoantigen (NeoAg) anti-CTLA-4 anti-PD-1 in preclinical models. Both NeoAg induce expansion intratumoral NeoAg-specific CD8 cells, though the degree acquisition effector activity was much more...
<div>Abstract<p>Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated 4 (CTLA-4) can provoke T cell–dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features cells require for efficacious ICT remain to be fully elucidated. Herein, we report anti–PD-1 anti–CTLA-4 induce upregulation the transcription factor BHLHE40 tumor...
Supplementary Figure from BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy
<div>Abstract<p>Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated 4 (CTLA-4) can provoke T cell–dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features cells require for efficacious ICT remain to be fully elucidated. Herein, we report anti–PD-1 anti–CTLA-4 induce upregulation the transcription factor BHLHE40 tumor...
Abstract The success of immune checkpoint therapy (ICT) in generating durable clinical responses is remarkable but not all cancer patients respond for reasons that are incompletely understood. In our previous studies to ICT the mouse T3 sarcoma model, we found strong upregulation BHLHE40 transcription factor a number cell populations. It was particularly prominent tumor antigen-specific CD8+ and CD4+ T cells, which crucial ICT-induced rejection elimination. We used global cell-type specific...
Abstract Effective cancer immunotherapy, such as immune checkpoint therapy (ICT) [e.g., anti-CTLA-4 and anti-PD-1/PD-L1], is dependent on T cell recognition of tumor antigens presented major histocompatibility complex (MHC) leads to durable responses in certain patients. Recent advances have facilitated identification mutant neoantigens led efforts develop effective personalized neoantigen vaccines. However, little known about how expression multiple with variable peptide-MHC (pMHC) binding...
Abstract Immune checkpoint therapy (ICT) (e.g. anti-CTLA-4, anti-PD-1) enables durable T-cell dependent anti-tumor immunity in patients with solid tumors. Since not all respond to ICT, this work aims at developing a more in-depth understanding of responses MHC class I (MHC-I) and II (MHC-II) tumor antigens that occur as consequence aberrant expression non-mutant or driver passenger mutations form neoantigens. We used poorly immunogenic Brafv600e Pten−/−Cdkn2a−/− YUMM1.7 (Y1.7) murine...