A5007307709- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Influenza Virus Research Studies
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- Mercury impact and mitigation studies
- Polyomavirus and related diseases
- Analytical chemistry methods development
- Systemic Lupus Erythematosus Research
- Bacteriophages and microbial interactions
- CRISPR and Genetic Engineering
- SARS-CoV-2 and COVID-19 Research
- Epigenetics and DNA Methylation
- Chromium effects and bioremediation
- Single-cell and spatial transcriptomics
- Microbial Natural Products and Biosynthesis
Sanofi (France)
2023-2025
National Cancer Institute
2015-2025
Center for Cancer Research
2011-2025
Sanofi (United States)
2015-2024
National Institutes of Health
2010-2024
Frederick National Laboratory for Cancer Research
2024
University of Calcutta
1990-2022
Royal Hospital for Sick Children
2020
Royal Hospital for Children
2020
All India Institute of Medical Sciences
2017
We identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating lymphocytes obtained from patient with metastatic colorectal cancer. observed objective regression of all seven lung metastases after the infusion approximately 1.11×1011 HLA-C*08:02-restricted that were composed four different clonotypes specifically targeted G12D. However, one these lesions had progressed on evaluation 9 months therapy. The lesion was resected and found to have lost chromosome 6...
It is unknown whether the human immune system frequently mounts a T cell response against mutations expressed by common epithelial cancers. Using next-generation sequencing approach combined with high-throughput immunologic screening, we demonstrated that tumor-infiltrating lymphocytes (TILs) from 9 out of 10 patients metastatic gastrointestinal cancers contained CD4(+) and/or CD8(+) cells recognized one to three neo-epitopes derived somatic patient's own tumor. There were no immunogenic...
The accurate identification of antitumor T cell receptors (TCRs) represents a major challenge for the engineering cell-based cancer immunotherapies. By mapping 55 neoantigen-specific TCR clonotypes (NeoTCRs) from 10 metastatic human tumors to their single-cell transcriptomes, we identified signatures CD8
Abstract Immunotherapies can mediate regression of human tumors with high mutation rates, but responses are rarely observed in patients common epithelial cancers. This raises the question whether these cancers harbor T lymphocytes that recognize mutant proteins expressed by autologous may represent ideal targets for immunotherapy. Using high-throughput immunologic screening gene products identified via whole-exome sequencing, we neoantigen-reactive tumor-infiltrating (TIL) from 62 75 (83%)...
PURPOSE Metastatic breast cancer (mBrCa) is most often an incurable disease with only modest responses to available immunotherapies. This study investigates the immunogenicity of somatic mutations in and explores therapeutic efficacy a pilot trial mutation-reactive tumor-infiltrating lymphocytes (TILs) patients metastatic disease. PATIENTS AND METHODS Forty-two mBrCa refractory previous lines treatment underwent surgical resection lesion(s), isolation TIL cultures, identification exomic...
Abstract T cells targeting shared oncogenic mutations can induce durable tumor regression in epithelial cancer patients. Such be detected infiltrating lymphocytes, but whether such the peripheral blood of patients with common metastatic is unknown. Using a highly sensitive vitro stimulation and cell enrichment memory from six patients, we identified isolated CD4 + , CD8 mutated KRAS G12D G12V variants, respectively, three In an additional two colon neoantigen-specific SMAD5 MUC4 proteins....
Tumor-resident lymphocytes can mount a response against neoantigens expressed in microsatellite-stable gastrointestinal (GI) cancers, and adoptive transfer of neoantigen-specific has demonstrated antitumor activity selected patients. However, whether peripheral blood could be used as an alternative minimally invasive source to identify targeting patients with GI cancer relatively low mutation burden is unclear. We personalized high-throughput screening strategy investigate PD-1 expression...
Adoptive cell therapy (ACT) with T cells targeting neoantigens can mediate durable responses in patients metastatic cancer. Cell therapies common shared antigens for epithelial cancers are not yet broadly available. Here, we report the identification and characterization one patient of T-cell receptors (TCRs) recognizing mutated p53 p.R175H, which is among a subset Tumor-infiltrating lymphocytes were screened recognition colorectal HLA-A*0201-restricted p.R175H was identified, minimal...
The adoptive transfer of neoantigen-reactive tumor-infiltrating lymphocytes (TILs) can result in tumor regression patients with metastatic cancer. To improve the efficacy T cell therapy targeting these tumor-specific mutations, we have proposed a new therapeutic strategy, which involves genetic modification autologous cells neoantigen-specific receptors (TCRs) and modified back to cancer patients. However, current techniques isolate TCRs are labor intensive, time consuming, technically...
<h3>Objective</h3> The standard therapy for advanced hepatocellular carcinoma (HCC) is sorafenib, with most patients experiencing disease progression within 6 months. Label-retaining cancer cells (LRCC) represent a novel subpopulation of stem (CSC). objective was to test whether LRCC are resistant sorafenib. <h3>Methods</h3> We tested human HCC derived and non-LRCC before after treatment <h3>Results</h3> from relatively proportion in cell lines increased sorafenib while the general...
The cofactor ATP stimulates the formation of T-antigen double hexamers on simian virus 40 core origin replication (I. A. Mastrangelo, P. V. C. Hough, J. S. Wall, M. Dodson, F. B. Dean, and Horwitz, Nature [London] 338:658-662, 1989). We report here pathway for assembly origin. triggers cooperative early late halves even when they are completely isolated. Hexamer nucleates at recognition pentanucleotides in half In intact origins, first hexamer cooperatively a second adjacent Thus,...
Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized result from either slow cycling or asymmetric cell division (ACD). However, the nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, that subpopulation LRCC is actively dividing exhibits pluripotency gene...
Abstract Purpose: Immunotherapies mediate the regression of human tumors through recognition tumor antigens by immune cells that trigger an response. Mutations in RAS oncogenes occur about 30% all patients with cancer. These mutations play important role both establishment and survival are commonly found hotspots. Discovering T-cell receptors (TCR) recognize shared mutated presented on MHC class I II molecules thus promising reagents for “off-the-shelf” adoptive cell therapies (ACT)...
Background Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, ex vivo expansion further reduce their frequencies. This complicates the identification T-cell receptors (TCRs) development TIL products with high reactivity patient treatment. Methods We tested whether could be in vitro...
The clinical burden caused by influenza can be mitigated the prophylactic use of seasonal vaccines. Their immunogen composition is revised biannually to optimally match antigenic drift hemagglutinin circulating virus strains. Antibodies directed against neuraminidase also correlate with protection influenza, yet evolution remains underexplored. To evaluate diversity N1 neuraminidase, we generated a panel immune sera 17 neuraminidases derived from human H1N1 strains that were isolated between...
The clinical burden caused by influenza can be mitigated the prophylactic use of seasonal vaccines. Their immunogen composition is revised biannually to optimally match antigenic drift hemagglutinin circulating virus strains. Antibodies directed against neuraminidase also correlate with protection influenza, yet evolution remains underexplored. To evaluate diversity N1 neuraminidase, we generated a panel immune sera 17 neuraminidases derived from human H1N1 strains that were isolated between...
Over 50% of patients with colorectal cancer (CRC) will progress and/or develop metastases. Biomarkers capable predicting progression, risk stratification and therapeutic benefit are needed. Cancer stem cells thought to be responsible for tumor initiation, dissemination treatment failure. Therefore, we hypothesized that CRC cell markers (CRCSC) identify a group at high progression.Paraffin-embedded tissue cores normal (n=8), histopathologically well-defined primary (n= 30) metastatic (n=10)...
Rapid industrialization and urbanization have contaminated the riverine estuarine ecosystems to a great extent. To evaluate such kind of contamination, we undertook research programme analyze concentrations zinc, copper, lead cadmium in muscle tissue five commonly edible shrimp species, namely Penaeus monodon, indicus, semisulcatus, marguensis Metapenaeus brevicornis collected from lower stretch River Ganga (in Sundarbans delta complex). The heavy metals samples were estimated using...