A5075533936- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Genetic factors in colorectal cancer
- Virus-based gene therapy research
- Melanoma and MAPK Pathways
- Radiopharmaceutical Chemistry and Applications
- Cancer Cells and Metastasis
- vaccines and immunoinformatics approaches
- Cell Adhesion Molecules Research
- CRISPR and Genetic Engineering
- Protease and Inhibitor Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Computational Drug Discovery Methods
- Protein Degradation and Inhibitors
- Protein Tyrosine Phosphatases
- Protein Kinase Regulation and GTPase Signaling
- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- T-cell and B-cell Immunology
- Neuroscience and Neuropharmacology Research
National Cancer Institute
2016-2025
Center for Cancer Research
2022-2025
National Institutes of Health
2014-2024
National Human Genome Research Institute
2009-2023
Data Harbor (United States)
2015
Cancer Genetics (United States)
2009-2014
Howard Hughes Medical Institute
2010
National Institute of Dental and Craniofacial Research
2010
Sidney Kimmel Cancer Center
2010
The University of Texas MD Anderson Cancer Center
2010
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...
Targeting nonviral antigens in viral-driven cancer Adoptive cell transfer harnesses a patient's own T cells to destroy cancer. The strategy can successfully treat epithelial tumors driven by human papillomavirus (HPV), but it remains unclear why only some patients respond. Stevanović et al. examined the antitumor response associated with HPV + cervical cancers that underwent complete regression. Unexpectedly, reactive were not directed against virally antigens, rather germline or neoantigens...
Adoptively transferred tumor-infiltrating T lymphocytes (TILs) that mediate complete regression of metastatic melanoma have been shown to recognize mutated epitopes expressed by autologous tumors. Here, in an attempt develop a strategy for facilitating the isolation, expansion, and study antigen-specific cells, we performed whole-exome sequencing on matched tumor normal DNA isolated from 8 patients with melanoma. Candidate were identified using peptide-MHC-binding algorithm, these...
BACKGROUND. Therapeutic vaccinations against cancer have mainly targeted differentiation antigens, cancer-testis and overexpressed antigens thus far resulted in little clinical benefit. Studies conducted by multiple groups demonstrated that T cells recognizing neoantigens are present most cancers offer a specific highly immunogenic target for personalized vaccination.
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%)...
Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) targeting neoantigens can mediate tumor regression in selected patients with metastatic epithelial cancer. However, effectively identifying and harnessing neoantigen-reactive T cells for patient treatment remains a challenge it is unknown whether current methods to detect are missing potentially clinically relevant neoantigen reactivities. We thus investigated the detection TILs could be enhanced by enriching that express...
Abstract Adoptive transfer of T cells with engineered T-cell receptor (TCR) genes that target tumor-specific antigens can mediate cancer regression. Accumulating evidence suggests the clinical success many immunotherapies is mediated by targeting mutated neoantigens unique to patient. We hypothesized most frequent TCR clonotypes infiltrating tumor were reactive against antigens. To test this hypothesis, we developed a multistep strategy involved TCRB deep sequencing CD8+PD-1+ subset,...
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...
Purpose: The adoptive transfer of lymphocytes genetically modified to express tumor reactive T-cell receptors (TCR) can mediate regression. Some tumor-infiltrating (TIL) recognize somatic mutations expressed only in the patient's tumors, and evidence suggests that clinically effective TILs target tumor-specific neoantigens. Here we attempted isolate neoantigen-reactive TCRs as a prelude treatment patients with autologous T cells such TCRs.Experimental Design: Mutations by tumors were...
Synonymous mutations, which do not alter the protein sequence, have been shown to affect function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683–691]. However, synonymous mutations are rarely investigated in cancer genomics field. We used whole-genome and -exome sequencing identify somatic 29 melanoma samples. Validation of one mutation BCL2L12 285 samples identified 12 cases that harbored recurrent F17F mutation. This led increased mRNA levels because differential targeting WT...
Summary Microphthalmia‐associated transcription factor (MITF) is involved in melanocyte cell development, pigmentation and neoplasia. To determine whether MITF somatically mutated melanoma, we compared the sequence of from primary metastatic lesions to patient‐matched normal DNA. In 50 melanoma tumor lines analysed, discovered four samples that had genomic amplifications mutations regions encoding transactivation, DNA binding or basic, helix‐loop‐helix domains. Sequence analysis for SOX10 ,...
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...
Abstract Purpose: This was a study prospectively evaluating intratumoral T-cell responses to autologous somatic mutated neoepitopes expressed by human metastatic ovarian cancers. Patients and Methods: Tumor-infiltrating lymphocytes (TIL) were expanded from resected cancer metastases, which analyzed whole-exome transcriptome sequencing identify mutations. All neoepitopes, independent of prediction algorithms, in antigen-presenting cells then cocultured with TIL fragment cultures. Secretion...
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...