A5077597600- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Immune Response and Inflammation
- Colorectal Cancer Treatments and Studies
- Immune Cell Function and Interaction
- Cancer Treatment and Pharmacology
- Heat shock proteins research
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- RNA Interference and Gene Delivery
- Nanoplatforms for cancer theranostics
- Chemokine receptors and signaling
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Photodynamic Therapy Research Studies
- Cancer, Hypoxia, and Metabolism
- Hepatocellular Carcinoma Treatment and Prognosis
- Wnt/β-catenin signaling in development and cancer
- Glycosylation and Glycoproteins Research
- Computational Drug Discovery Methods
- Infrared Thermography in Medicine
Rakuten (United States)
2024
University of Yamanashi
2024
Duke Medical Center
2014-2023
Duke University
2013-2023
Rakuten (Japan)
2023
Duke University Hospital
2010-2022
Duke Cancer Institute
2021
University of California, San Francisco
2012
Middlesex University
2011
Carolina BioOncology Institute
2011
BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of narrow spectrum cell proteins represent novel platform for delivering antigen in conjunction with costimulatory molecules. We performed this study test the safety, feasibility and efficacy autologous dendritic (DC)-derived exosomes (DEX) loaded MAGE tumor antigens patients non-small lung (NSCLC). METHODS: This Phase I enrolled HLA...
Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting diminished downstream β-catenin signaling. In this study, we determined whether could inhibit human CRCs and its inhibition might elicit antitumor effects presence APC mutations. We found that inhibited...
Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs), known to inhibit cyclooxygenase (COX), reduce the risk of colorectal cancer. COX is a key enzyme in prostaglandin biosynthesis, and two isoforms COX, COX-1 COX-2, been identified. Recently COX-2 has reported frequently overexpress neoplasms play role tumorigenesis tumour progression. In this study, using immunohistochemistry, we examined expression advanced human cancer its correlation with...
The cell surface proteoglycan, chondroitin sulfate proteoglycan 4 (CSPG4), is a potential target for monoclonal antibody (mAb)-based immunotherapy many types of cancer. lack effective therapy triple-negative breast cancer (TNBC) prompted us to examine whether CSPG4 expressed in TNBC and can be targeted with CSPG4-specific mAb.CSPG4 protein expression was assessed 44 primary lesions, lines HS578T, MDA-MB-231, MDA-MB-435, SUM149, tumor cells pleural effusions from 12 metastatic patients....
The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); however, targeting tumor antigen directly APC in would a less strategy. We wished test whether targeted delivery an otherwise poorly immunogenic, soluble through their mannose receptors (MR) induce clinically relevant immunity.Two phase I studies were...
Abstract Introduction The human epidermal growth factor receptor 2 ( HER2 ) tyrosine kinase (RTK) oncogene is an attractive therapeutic target for the treatment of HER2-addicted tumors. Although lapatinib, FDA-approved small-molecule and (EGFR) inhibitor (TKI), represents a significant advancement in + breast cancers, responses to lapatinib have not been durable. Consequently, elucidation mechanisms acquired resistance HER-directed therapies critical importance. Methods Using functional...
Abstract HER2 overexpression occurs in approximately 25% of breast cancers, where it correlates with poor prognosis. Likewise, systemic inflammation cancer prognosis, although the process is not understood. In this study, we explored relationship between and inflammation, comparing effects overexpressing wild-type or mutated inactive forms primary human cells. Wild-type elicited a profound transcriptional inflammatory profile, including marked elevation interleukin-6 (IL-6) expression, which...
In Brief Objective: To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) MUC1 (PANVAC) would lengthen survival in patients with resected metastases colorectal cancer (CRC). Background: Recurrences after complete resections metastatic CRC remain frequent. Immune responses to are associated fewer recurrences, suggesting a role for as adjuvant therapy. Both DCs potent stimulators immune against antigens. Methods: Patients,...
Despite multimodal adjuvant management with radiotherapy, chemotherapy and hormonal therapies, most surgically resected primary breast cancers relapse or metastasize. A potential solution to late distant recurrence is augment systemic antitumor immunity, in part by appropriately presenting tumor antigens, but also modulating the immunosuppressive microenvironment (TME). We previously validated this concept models of murine carcinoma treated a novel predominately microcavitating version...
Abstract Purpose: To determine the safety and immunologic clinical efficacy of a dendritic cell vaccine modified to hyperexpress costimulatory molecules tumor antigen. Experimental Design: In this phase I study, we administered one or two cycles four triweekly s.c./intradermal injections ex vivo generated cells with recombinant fowlpox vector encoding carcinoembryonic antigen (CEA) triad [rF-CEA(6D)-TRICOM]. Controls consisted immature loaded tetanus toxoid HLA A2–restricted peptide derived...
Therapeutic anticancer vaccines are designed to boost patients' immune responses tumors. One approach is use a viral vector deliver antigen in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific neutralizing antibodies suppressive populations such as Tregs remain great challenges the efficacy of this approach. We report here that an alphavirus vector, packaged virus-like replicon particles (VRP) capable efficiently infecting could be...
Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccines induce polyclonal responses against HER2 that demonstrate enhanced anti-tumor activity when combined lapatinib in murine models. We wished to test clinical safety, immunogenicity, of a cancer vaccine, lapatinib.We immunized women (n = 12) metastatic,...
The human growth factor receptor type 2 (HER2) is overexpressed in breast as well other types of cancer. Immuno-PET, a noninvasive imaging procedure that could assess HER2 status both primary and metastatic lesions simultaneously, be valuable tool for optimizing application HER2-targeted therapies individual patients. Herein, we have evaluated the tumor-targeting potential 5F7 anti-HER2 Nanobody (single-domain antibody fragment; ∼13 kDa) after <sup>18</sup>F labeling by methods....
Pompe disease can be treated effectively, if immune tolerance to enzyme replacement therapy (ERT) with acid α-glucosidase (GAA) is present. An adeno-associated viral (AAV) vector carrying a liver-specific regulatory cassette drive GAA expression (AAV-LSPhGAA) established in knockout (KO) mice, whereas ubiquitous AAV-CBhGAA provoked responses. Therefore, we investigated the hypothesis that induced by hepatic-restricted was dominant. AAV-LSPhGAA and were administered singly or combination...
Abstract Purpose: Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines targeting established oncogenic drivers such as the genomic amplification HER2. We constructed a vaccine based on novel alphaviral vector encoding portion HER2 (VRP-HER2). Patients and Methods: In preclinical studies, mice were immunized VRP-HER2 before or after...
The Wnt signaling pathway, known for regulating genes critical to normal embryonic development and tissue homeostasis, is dysregulated in many types of cancer. Previously, we identified that the anthelmintic drug niclosamide inhibited by promoting internalization receptor Frizzled 1 degradation pathway proteins, Dishevelled 2 β-catenin, contributing suppression colorectal cancer growth vitro vivo Here, provide evidence niclosamide-mediated inhibition mediated through autophagosomes induced...
Abstract Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) have entered the landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness critically needed. Patients Methods: Using mouse models we evaluate immune activation tumor intratumoral IL12 plasmid followed by...
Abstract Background. Degradation of basement membrane and extracellular matrix by metalloproteinases (MMPs) is believed to be an essential step in the complicated process hematogenous metastasis. MMP-1 a member collagenases, family MMPs that degrades collagens type I, II, III, main components interstitial stroma. The purpose this study was investigate expression colorectal cancer its correlation with Patients Methods. We examined 133 cases (Dukes A: 72; Dukes B: 26; C: 23; D: 12). Sections...