NATIONAL CANCER INSTITUTE - CANCER.GOV

Contact Information

Primary Contact

Shyam Sharan
Scientific Director

Location

Building 469, NCI-Frederick
Frederick, MD 21703

Additional Contacts

Ken Miller
Program Manager

Overview

The Center for Advanced Preclinical Research (CAPR) specializes in evaluating the efficacy of preclinical compounds, existing drugs, or biologics (therapeutics) in genetically engineered mouse (GEM) models, GEM-derived allograft (GDA) models, or patient-derived mouse xenografts (PDX). We partner primarily with Center for Cancer Research (CCR) investigators and clinicians using an RFA mechanism described below. Projects outside of CCR may be considered on a case-by-case basis.

List of Services

One of the key features that distinguishes preclinical studies performed at CAPR is the use of immune-proficient genetically engineered mouse models (A detailed list can be found here: https://ccr.cancer.gov/center-for-advanced-preclinical-research/capr-models). Importantly, we leverage our large, diverse mouse colony and access to advanced tumor imaging modalities to breed, randomize, and enroll statistically powered study cohorts that yield more clinically predictive results than smaller studies can achieve.

Our expertise includes the development of novel GEM-derived allograft models (GDA) that are well suited for preclinical studies.

The range and scope of projects vary from testing the tolerability and efficacy of therapeutic compounds or cell-based therapeutics, to the development and characterization of novel cancer mouse models, and participating in co-clinical trials for simultaneous evaluation of drug response in patients and in mouse models, including generation of patient-derived xenografts (PDXs).

Our board-certified pathologist performs thorough biomarker characterization on in-house generated immunohistochemistry (IHC) and immunofluorescent (IF) stained sections utilizing AI-supported automated high-content image analyses and quantification tools available at CAPR.

We work closely with all core facilities on both Frederick campuses.

Select publications illustrating our capabilities can be found here: https://ccr.cancer.gov/center-for-advanced-preclinical-research/capr-publications

Established Technologies/Instrumentation

Genetically Modified Mouse Models

A detailed list of CAPR cancer mouse models can be found here: https://ccr.cancer.gov/center-for-advanced-preclinical-research/capr-publications

In Vivo Capabilities

  • Characterization and validation of GEM models
  • GEM model re-tooling/refinement and GEM engineering
  • Adaptation of GEM models to syngeneic allograft models
  • Surgical techniques for the generation of murine orthotopic transplant model cohorts
  • Pharmacokinetics and biodistribution of therapeutics in animal models
  • Pharmacodynamics: evaluation of drug effect on the intended target in tumor tissue
  • Evaluation of therapeutic candidates in large, well-controlled efficacy studies
  • Cancer prevention studies in GEM models
  • Imaging modalities (MRI, PET/CT, ultrasound, and bioluminescence) and real-time tumor volume measurements based on live imaging utilizing Frederick-based LASP SAIC core
  • Biomarkers/molecular signatures of treatment response:
    • Immunohistochemical stains
    • Transcriptome
    • Metabolome
  • Generation of novel PDX models from patient tissue

In Vitro Capabilities

  • Primary tumor cell culture establishment
  • CRISPR and recombineering allele construction
  • Histopathological assessment
  • Quantitative molecular pathology
  • Evaluation of drug target inhibition
  • Establishment of primary tumor cell culture from GEM, GDA, or PDX models
  • Evaluation of drug potency in primary tumor cells/specific target validation assays

User Guidelines

CAPR is not a Core and does not accept requests as such. Each year, we onboard new projects through a CCR-wide request for application (RFA) announcement (a sample RFA document is here: https://ccrod.cancer.gov/confluence/display/CC/2021+RFA). The CAPR Oversight Committee, in consultation with CAPR scientists, reviews and scores the proposals to select 5-8 new projects for their scientific merit, novelty, feasibility, and potential to accelerate cancer treatment, prevention or detection. These projects can vary widely in scope but take an average of about 18 months to complete. We may also carry out isolated pilot or proof of concept studies when appropriate and as workload allows.

Please reach out to the contacts above for more information.

Publications

  • Jaynes J, Sable R, Ronzetti M, Bautista-Guzman W, Knotts Z, Abisoye-Ogunniyan A, Li d, Calvo R, Dashnyam M, Singh A, Guerin T, White J, Ravichandran S, Kumar P, Talsania K, Chen V, Ghebremedhin A, Karanam B, Bin Salam A, Amin R, Odzorig T, Aiken T, Nguyen V, Bian Y, Zarif J, de Groot A, Mehta M, Fan L, Hu X, Simeonov A, Pate N, Abu-Asab M, Ferrer M, Southall N, Ock C-Y, Zhao Y, Lopez H, Kozlov S, de Val N, Yates C, Baljinnyam B, Marugan J, Rudloff U. Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate anti-tumor immune responses. Science Translational Medicine. 2020 Feb 12; Vol. 12, Issue 530. DOI:10.1126/scitranslmed.aax6337 PMID: 32051227
  • Pérez-Guijarro E, Yang HH, Araya RE, El Meskini R, Michael HT, Vodnala SK, Marie KL, Smith C, Chin S, Lam KC, Thorkelsson A, Iacovelli AJ, Kulaga A, Fon A, Michalowski AM, Hugo W, Lo RS, Restifo NP, Sharan SK, Van Dyke T, Goldszmid RS, Weaver Ohler Z, Lee MP, Day CP, Merlino G. Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy. Nat Med. 2020 May 26 (5):781-791. DOI:10.1038/s41591-020-0818-3. PMID: 32284588
  • El Meskini R, Atkinson D, Kulaga A, Abdelmaksoud A, Gumprecht M, Pate N, Hayes S, Oberst M, Kaplan IM, Raber P, Van Dyke T, Sharan SK, Hollingsworth R, Day C-P, Merlino G, Weaver Ohler Z. Distinct Biomarker Profiles and TCR Sequence Diversity Characterize the Response to PD-L1 Blockade in a Mouse Melanoma Model. Molecular Cancer Research; Published Online First April 22, 2021; DOI: 10.1158/1541-7786. MCR-20-0881
  • Hagerty B, O’Sullivan TN, Zhang X, Collins NK, Custer Lawrence W, Bassel LL, Pate N, Xu J, Guerin TM, Kozlov S and Alewine C. Novel humanized mesothelin-expressing genetically engineered mouse models underscore challenges in delivery of complex therapeutics to pancreatic cancers. Mol Cancer Ther July 26 2021 DOI: 10.1158/1535-7163.MCT-21-0017
  • Li D, Schaub N, Guerin TM, Bapiro TE, Richards FM, Chen V, Talsania K, Kumar P, Gilbert DJ, Schlomer JJ, Kim SJ, Sorber R, Teper Y, Bautista W, Palena C, Ock CY, Jodrell DI, Pate N, Mehta M, Zhao Y, Kozlov S, Rudloff U. T Cell-Mediated Antitumor Immunity Cooperatively Induced By TGFβR1 Antagonism and Gemcitabine Counteracts Reformation of the Stromal Barrier in Pancreatic Cancer. Mol Cancer Ther. 2021 Oct;20(10):1926-1940. DOI: 10.1158/1535-7163.MCT-20-0620. Epub 2021 Aug 10. PMID: 34376576; PMCID: PMC8492543.

Keywords

AllograftBRCAGEMMMelanomaMouseNSCLCPDACPDXPancreaticPreclinicalSCLCAnimal Resourcesglioblastomimmunocompetentlung cancermammarynci-ncrovarian