A5055988161- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- Bacteriophages and microbial interactions
- Cancer Cells and Metastasis
- Synthesis and biological activity
- Cancer Mechanisms and Therapy
- Reproductive Health and Technologies
- Lung Cancer Research Studies
- Immune cells in cancer
- Synthesis and Characterization of Heterocyclic Compounds
- Immune Cell Function and Interaction
- Health and Medical Studies
- Evolutionary Psychology and Human Behavior
- vaccines and immunoinformatics approaches
- Exercise and Physiological Responses
- SARS-CoV-2 and COVID-19 Research
- Enzyme function and inhibition
- Gastric Cancer Management and Outcomes
- Assisted Reproductive Technology and Twin Pregnancy
Drexel University
2025
Dana-Farber Cancer Institute
2017-2023
Center for Orthopaedics
2023
Boston College
2015-2018
Krajská Nemocnice Liberec
1990
Abstract Small cell lung carcinoma (SCLC) is highly mutated, yet durable response to immune checkpoint blockade (ICB) rare. SCLC also exhibits cellular plasticity, which could influence its immunobiology. Here we discover that a distinct subset of uniquely upregulates MHC I, enriching for ICB benefit. In vitro modeling confirms epigenetic recovery I in following loss neuroendocrine differentiation, tracks with derepression STING. Transient EZH2 inhibition expands these nonneuroendocrine...
We developed a screening assay in which luciferized ID8 expressing OVA was cocultured with transgenic CD8+ T cells specifically recognizing the model antigen an H-2b-restricted manner. The screened small-molecule library to identify compounds that inhibit or enhance cell-mediated killing of tumor cells. Erlotinib, EGFR inhibitor, top compound enhanced T-cell Subsequent experiments erlotinib and additional inhibitors validated screen results. increased both basal IFNγ-induced MHC class-I...
Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for EGFR-mutant non–small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of ERBB family that functions by dimerizing with other members (EGFR and HER2) frequently overexpressed in NSCLC. Although TKI mechanisms do not lead alterations HER3, we hypothesized targeting might improve efficacy...
Resistance to oncogene-targeted therapies involves discrete drug-tolerant persister cells, originally discovered through in vitro assays. Whether a similar phenomenon limits efficacy of programmed cell death 1 (PD-1) blockade is poorly understood. Here, we performed dynamic single-cell RNA-Seq murine organotypic tumor spheroids undergoing PD-1 blockade, identifying subpopulation immunotherapy cells (IPCs) that resisted CD8+ T cell-mediated killing. These expressed Snai1 and stem antigen...
Abstract Purpose: Evaluating drug responses using primary patient-derived cells ex vivo represents a potentially rapid and efficient approach to screening for new treatment approaches. Here, we sought identify neratinib combinations in HER2 mutant non–small cell lung cancer (NSCLC) patient xenograft-derived organotypic spheroids (XDOTS) short-term system. Experimental Design: We generated two HER2-mutant NSCLC PDX models [DFCI359 (HER2 exon19 755_757LREdelinsRP) DFCI315 exon20...
MET-targeted therapies are clinically effective in MET-amplified and MET exon 14 deletion mutant (METex14) non-small cell lung cancers (NSCLCs), but their efficacy is limited by the development of drug resistance. Structurally distinct tyrosine kinase inhibitors (TKIs) (type I/II) have been developed or under clinical evaluation, which may overcome MET-mediated resistance mechanisms. In this study, we assess secondary mutations likely to emerge response treatment with single-agent...
Abstract As immune checkpoint blocking antibodies increasing become foundational therapies for the treatment of cancer, there is a pressing need to identify compounds that synergize with blockade as basis combinatorial regimens. We have developed screening assay in which luciferized tumor cell line expressing model antigen co-cultured transgenic CD8+ T specifically recognizing H-2b-restricted manner. The target cell/T was screened small molecule library inhibit or enhance cell-mediated...
Mycoplasmas are the smallest, self‐replicating free‐living prokaryotes, and have been associated with carcinogenesis. can be detected in a large percentage wide variety of primary human cancers. Some mycoplasma species such as M. fermentans hyorhinis transform normal murine cell lines into tumorigenic cells. Mycoplasma infection activate oncogenes well inactivate tumor suppressor genes suggesting that mycoplasmas both carcinogenic or onco‐modulatory. PCR amplification sequencing showed...
<div>Abstract<p>Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for <i>EGFR</i>-mutant non–small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of ERBB family that functions by dimerizing with other members (EGFR and HER2) frequently overexpressed in NSCLC. Although TKI mechanisms do not lead alterations HER3, we...
<p>Supplemental Figure 3. Tumor volumes (TV; mean +/- SEM) over time of PDX DFCI 359 and 315 dosed with neratinib (40mg/kg daily), TDM1 (20 mg/kg weekly), their combinations (n = 8 mice/cohort). The data for the vehicle arms are from same experiment as in 5D.</p>
<p>Supplemental Legend</p>
<p>Supplemental Figure 4. Change in body weight over time HER2 YVMA GEMs treated with neratinib alone or combination trastuzumab.</p>
<p>Supplemental Figure 2. Orthogonal assays for cell viability in drug resistant models.</p>
<p>Supplemental Legend</p>
<p>Supplemental Figure 1. Characterization of DFCI 359 and 315.</p>