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Principal Investigator: Liang Cao
Organization: DIVISION OF BASIC SCIENCES - NCI
Fiscal Year: 2022
Award: $822,832
Funding agency: National Cancer Institute
Related to the specific biomarker goals above, we conducted various studies to support biomarker driven early-stage drug development: 1. Application of new or novel biomarkers in early-stage trials of highly unique therapeutic agents. A) We supported correlative marker investigations of Dr. Raffit Hassan on his mesothelin-targeted novel therapies, including traditional antibody drug conjugate therapies, and T cell therapies, using the assay that we have previously developed (JCO Precis Oncol. doi: 10.1200/PO.17.00282, 2018). Significant responses were seen in many patients, where our tumor antigen tests were performed in near real time to provide investigators with timely information on responses and on progression. B) We provided continues biomarker support of clinical trials by Dr. Andrea Apolo and some of the work was published (Girardi DM, Clin Cancer Res, doi: 10.1158/1078-0432. 2022). C) We developed a cell free DNA detection for cervical cancer and use it for treatment monitoring, minimum residue disease (MRD) detection, cancer genotyping for patient selection. We support HPV-targeted therapy trials by Dr. Scott Norberg. Some of the recent work was focused on using NGS with cell free DNA for resistance mechanisms against T cell therapies. D) Somatic mutation analysis with cell free DNA in pregnant women with abnormal chromosome test results. In working with Christina Annunziata and Dr. Diana Bianchi of NICHD, we performed some pioneer work to uncover tumor specific somatic mutation informing on cancer origins, on common pathogenic processes, and on treatment drug options. Interim results presented some significant novel knowledge in the field which could impact the patient clinical management, and inform on the feasibility of using chromosome aneuploidy for cancer screening. 2. Identification of new biomarkers. A) In working with Dr. Steven Pavletic, we developed new cytokine tests for the investigation of graft vs host disease (Curtis LM Blood. 137:896-907. 2021; Goklemez S Bone Marrow Transplant. doi: 10.1038/s41409-021-01419-2. 2021). B) Preclinical investigation of tumor biomarker in animal models. The work with Dr. Christine Alewine is to better design the clinical study and to improve the value of the biomarker investigation. Some of the research was published (Zhang X, Transl Oncol, doi: 10.1016/j.tranon.2022.101440. 2022), with others to follow. 3. Assay development and validation. A) In response to COVID-19 pandemic, we developed a high-performance serology test for COVID-19. In addition, we also developed a test to evaluate an assay to evaluate the ACE2 receptor binding of various SARS-cov-2 variants. We generated extensive clinical data with donors who had COVID-19 or vaccination in collaboration with Dr. Kamille West of NIH Clinical Center (Yu Y, Sci Rep, 12:2628. doi: 10.1038/s41598-022-06629-2. 2022). 4. New technology development. A) We focus on the development of a circulating tumor DNA based technology for determining cancer gene mutations associated with treatment responses, and for the identification of mutations associated with resistance. We successfully developed new NGS-based assays to examine somatic mutations involved in the process of antigen presentation and T cell response using cell free DNA. The work is to support trials by Dr. Christian Hinrichs, who was succeeded by Dr. Scott Norberg. B) We are working on cell free DNA test for the investigation of potential neoplasia in pregnant women presented with abnormal NIPT test results in a trial led by Dr. Christina Annunziata and Dr. Diana Bianchi of NICHD.
Terms: <2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><ACE2><Aberrant Chromosome><Aneuploid><Aneuploidy><Animal Model><Animal Models and Related Studies><Antibody-drug conjugates><Antigen Presentation><Assay><Bioassay><Biologic Assays><Biological Assay><Biological Markers><Blood><Blood Reticuloendothelial System><Bone Marrow Grafting><Bone Marrow Transplant><Bone Marrow Transplantation><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 public health crisis><COVID-19 test><COVID-19 tests><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID19><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 public health crisis><COVID19 test><COVID19 tests><CV-19><CV19><Cancer Gene Mutation><Cancer Screening for Patients><Cancers><Cervical Cancer><Cervix Cancer><Chromosomal Aberrations><Chromosomal Abnormalities><Chromosomal Alterations><Chromosome Aberrations><Chromosome Alterations><Chromosome Anomalies><Chromosome abnormality><Chromosomes><Clinical Data><Clinical Drug Development><Clinical Drug Testing/Development><Clinical Management><Clinical Research><Clinical Study><Clinical Trials><Collaborations><Cytogenetic Aberrations><Cytogenetic Abnormalities><Data><Detection><Development><Disease><Disorder><Dose><Drug Kinetics><Drugs><Evaluation><Experimental Therapies><Genetic Alteration><Genetic Change><Genetic defect><Goals><GvHD><HPV><Homologous Wasting Disease><Human Papilloma Virus><Human Papillomavirus><Immune response><Immunological response><Infectious Human Wart Virus><Investigation><Investigational Therapies><Investigational Treatments><Investigators><Knowledge><Laboratories><Malignant Cervical Neoplasm><Malignant Cervical Tumor><Malignant Neoplasm of the Cervix><Malignant Neoplasms><Malignant Tumor><Malignant Tumor of the Cervix><Malignant Tumor of the Cervix Uteri><Malignant Uterine Cervix Neoplasm><Malignant Uterine Cervix Tumor><Malignant neoplasm of cervix uteri><Marrow Transplantation><Medication><Monitor><Mutation><Mutation Analysis><NICHD><NIH><National Institute of Child Health and Human Development><National Institute of Children's Health and Human Development><National Institutes of Health><Neoplasms><Pathogenicity><Patient Monitoring><Patient Selection><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Performance><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacodynamics><Pharmacokinetics><Phase><Pregnant Women><Process><Publishing><Research><Research Personnel><Researchers><Resistance><Runt Disease><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 test><SARS-CoV-2 tests><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2 epidemic><SARS-CoV2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Screening for cancer><Serology test><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Soluble Mpf/Mesothelin-Related Protein><Somatic Mutation><T cell based therapeutics><T cell based therapy><T cell directed therapies><T cell response><T cell targeted therapeutics><T cell therapy><TM-MKR><Technology><Test Result><Testing><Therapeutic><Therapeutic Agents><Time><Tumor Antigens><Tumor Markers><Tumor-Associated Antigen><United States National Institutes of Health><Uterine Cervix Cancer><Vaccination><Validation><Work><adoptive T cell transfer><adoptive T-cell therapy><angiotensin converting enzyme 2><angiotensin converting enzyme II><antigen based test><antigen test><assay development><base><bio-markers><biologic marker><biomarker><biomarker-driven><cancer antigens><cancer specific gene mutation><cell free DNA><cell free circulating DNA><chromosomal defect><chromosome defect><clinical center><clinical development><clinical investigation><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 test><coronavirus disease 2019 tests><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><cytokine><design><designing><developmental><drug development><drug/agent><early biomarkers><early cancer detection><early detection biomarkers><early detection markers><expectant mother><expecting mother><experimental therapeutic agents><experimental therapeutics><genome mutation><genotyped patients><graft versus host disease><graft vs host disease><graft vs. host disease><host response><immune system response><immunoresponse><improved><malignancy><mesothelin><model of animal><model organism><neoplasia><neoplasm/cancer><neoplastic growth><new drug target><new druggable target><new marker><new pharmacotherapy target><new technology><new therapeutic target><new therapy target><novel><novel biomarker><novel drug target><novel druggable target><novel marker><novel pharmacotherapy target><novel technologies><novel therapeutic target><novel therapy target><patient safety><pre-clinical><preclinical><pregnant mothers><receptor binding><receptor bound><resistance mechanism><resistant><resistant mechanism><response><response to therapy><response to treatment><serology assay><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 test><severe acute respiratory syndrome coronavirus 2 tests><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><specific biomarkers><targeted drug trials><targeted pharmaceutical trials><targeted therapy trials><targeted treatment trials><tech development><technology development><therapeutic T-cell platform><therapeutic response><therapy response><treatment response><tumor><tumor DNA><tumor biomarker><tumor cell DNA><tumor specific biomarker><tumor-specific DNA><tumor-specific antigen><wart virus>