A5002046107- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Immunotherapy and Biomarkers
- Antiplatelet Therapy and Cardiovascular Diseases
- Nanowire Synthesis and Applications
- Virus-based gene therapy research
- Ion Channels and Receptors
- Immune Cell Function and Interaction
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Inflammatory mediators and NSAID effects
- Platelet Disorders and Treatments
- Cancer Cells and Metastasis
- Organophosphorus compounds synthesis
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Neurobiology and Insect Physiology Research
- Silicon Carbide Semiconductor Technologies
- Neuropeptides and Animal Physiology
- Cytokine Signaling Pathways and Interactions
- Biochemical Analysis and Sensing Techniques
- Advancements in Semiconductor Devices and Circuit Design
- Venous Thromboembolism Diagnosis and Management
- Synthesis of β-Lactam Compounds
- Apelin-related biomedical research
City of Hope
2013-2024
Beckman Research Institute
2013-2024
City Of Hope National Medical Center
2014-2024
Western University of Health Sciences
2010-2013
Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due absence of truly restricted antigen expression potential safety concerns "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells treatment metastases, determined optimal second-generation route administration xenograft mouse models metastatic tumors, including multifocal...
An effective combination immunotherapy using oncolytic viruses delivers de novo CD19 to promote CD19-CAR T cell therapy against solid tumors in mice.
Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains lethal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated durable remissions in hematological malignancies. We report results from a phase 1, first-in-human study of stem (PSCA)-directed CAR cells men with mCRPC. The starting dose level (DL) was 100 million (M) without lymphodepletion (LD), followed by incorporation LD. primary end points were safety and dose-limiting...
Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in field immunotherapy, given impressive recent clinical responses hematological malignancies. Prostate cancer may be amenable to cell-based immunotherapy since several tumor antigens, including prostate stem-cell (PSCA), are widely over-expressed metastatic disease. While selectivity CARs crucial, it problematic due absence truly restricted expression and potential...
Impressive clinical efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy for hematological malignancies have prompted significant efforts in achieving similar responses solid tumors. The lack truly restricted and uniform expression tumor-associated antigens, as well limited persistence and/or tumor trafficking pose major challenges successful translation CAR Recent studies demonstrated that aberrantly glycosylated surface proteins on cells are amenable targets....
Chimeric antigen receptor (CAR) T cell therapy has led to impressive clinical responses in patients with hematological malignancies; however, its effectiveness solid tumors been limited. While CAR cells for the treatment of advanced prostate and pancreas cancer, including those targeting stem (PSCA), are being clinically evaluated anticipated show bioactivity, their safety impact immunosuppressive tumor microenvironment (TME) have not faithfully explored preclinically. Using a novel human...
Abstract Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited trafficking, persistence, and durable anti-tumor activity in solid tumors. However, these challenges can be largely overcome relatively unconstrained synthetic engineering strategies. Here, we describe CAR cells targeting tumor-associated glycoprotein-72 (TAG72), utilizing the CD28 transmembrane domain upstream of 4-1BB co-stimulatory as a driver potent IFNγ secretion. cell-mediated production...
Abstract The tumor microenvironment is composed of heterogeneous populations cells, including cancer, immune, and stromal cells. Progression growth initiation metastasis critically dependent on the reciprocal interactions between cancer cells stroma. Through RNA-Seq protein analyses, we found that cancer-associated fibroblasts derived from human breast brain express significantly higher levels chemokines CXCL12 CXCL16 than primary tumors or normal breast. To further understand interplay each...
Antiplatelet therapy has been documented to reduce risks of cardiovascular disease after acute myocardial infarction, coronary artery bypass graft, and in chronic atrial fibrillation patients, amongst other risk factors. Conventional management thrombosis-based disorders includes the use heparin, oral anticoagulants, preferred antiplatelet agent aspirin. Interestingly, aspirin was not intended be used as an agent; rather, being repurposed, it become one most widely prescribed antithrombotic...
CAR T cell efficacy in solid tumors is limited due part to the immunosuppressive TME. To improve anti-tumor responses, we hypothesized that enabling cells secrete bifunctional fusion proteins consisting of a cytokine modifier (e.g., TGFβtrap, IL15, or IL12) combined with an immune checkpoint inhibitor αPDL1) will provide tumor localized immunomodulation functionality. end, engineered IL12 molecules fused αPDL1 scFv, and assessed vitro functionality vivo safety prostate ovarian cancer models....
Current vaccine conditions predominantly elicit low-avidity cytotoxic T lymphocytes (CTLs), which are non-tumor-cytolytic but indistinguishable by tetramer staining or enzyme-linked immunospot from high-avidity CTLs. Using CTL clones of high low avidity for melanoma antigens, we show that CTLs can inhibit tumor lysis in an antigen-specific manner. This phenomenon operates vivo: control growth animals not combination with specific the same antigen. The mechanism involves stripping...
The premise of targeted therapy was born from an intimate understanding the unique biological pathways and endpoints which are implicated in development different disease states conditions. In addition, identification most appropriate drugs to use for drug has aided growing interest pharmaceutical industry allocate more resources monoclonal antibody (mAb) therapeutics. This being case, it is important understand based therapeutics, some currently Food Drug Administration (FDA)-approved mAbs...
Advancing chimeric antigen receptor (CAR)-engineered T cells for the treatment of solid tumors is a major focus in field cellular immunotherapy. Several hurdles have hindered similar CAR cell clinical responses as seen hematological malignancies. These challenges include on-target off-tumor toxicities, which inspired efforts to optimize CARs improved tumor selectivity and overall safety. We recently developed therapy targeting prostate stem (PSCA) pancreatic cancers, showing preclinical...
Abstract Background: There is growing evidence that responsiveness to immunotherapy influenced by the composition of a patient’s gut microbiota. Recent analysis identified strong correlations between abundance microbial species and positive response immune based therapies in cancer patients. Further, enrichment commensal microbes can promote immunostimulatory effects, anti-tumor responses, increased cytotoxic T cell within TME. Conversely, presence known cause inflammatory states tissues may...
Objective: The purpose of this study is to investigate the potential in vivo antiplatelet and thromboprotective properties antihypertensive drug losartan mice. Methods: Aggregometry studies were performed on platelets obtained from mice administered for 5 days, via tail vein examine ex effects (dose dependence) agent select an appropriate dose studies. Next, bleeding time test occlusion a carotid artery injury thrombosis model (ferric chloride) also assess treatment. Results: These data...
Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited trafficking, persistence, and durable anti-tumor activity in solid tumor microenvironments. However, these challenges can be largely overcome relatively unconstrained synthetic engineering strategies, which being harnessed to improve CAR therapies. Here, we describe fully optimized cells targeting tumor-associated glycoprotein-72 (TAG72) for the treatment of tumors, identifying CD28 transmembrane domain...
Abstract Chimeric antigen receptor (CAR)-engineered T cell therapy for solid tumors is limited by the lack of tumor-restricted and homogeneous expression tumor antigens 1,2 . Therefore, we engineered an oncolytic virus to express a non-signaling, truncated CD19 (CD19t) protein tumor-selective delivery, enabling targeting CD19-specific CAR cells. Infecting cells with chimeric vaccinia coding CD19t (OV19t) produced de novo surface-antigen prior virus-mediated lysis. Co-cultured CD19-CAR...
Abstract Background: Success of Chimeric Antigen Receptor (CAR) T cells therapy for solid tumors are limited by the suppressive tumor microenvironment (TME), cell exhaustion, lack persistence, and poor trafficking to tumors. Strategies improve this include therapeutic combinations, such as checkpoint inhibition (CPI) or cytokine support. However, CPI has largely failed because refractory resistant administration can lead lethal toxicities. To end, we propose that enabling CAR secrete...
Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells has demonstrated robust and durable clinical efficacy in patients with CD19+ B-cell malignancies. Broader application this approach to brain other advanced solid tumors is an immediate goal for the field presently under intense investigation. In 2014, 40,000 individuals U. S. alone succumbed breast cancer, primarily as a result metastatic disease. Approximately 30 percent cancer carry amplification HER2 gene and/or...