Genetically Engineered Mouse Models of Pancreatic Cancer: The KPC Model (LSL‐KrasG12D/+;LSL‐Trp53R172H/+;Pdx‐1‐Cre), Its Variants, and Their Application in Immuno‐oncology Drug Discovery

Jae W. Lee1, Chad A. Komar1, Fee Bengsch1, Kathleen Graham1, Gregory L. Beatty1

1 Division of Hematology‐Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 14.39
DOI:  10.1002/cpph.2
Online Posting Date:  June, 2016
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Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer‐related deaths in the United States. For patients with unresectable disease, treatment options are limited and lack curative potential. Preclinical mouse models of PDAC that recapitulate the biology of human pancreatic cancer offer an opportunity for the rational development of novel treatment approaches that may improve patient outcomes. With the recent success of immunotherapy for subsets of patients with solid malignancies, interest is mounting in the possible use of immunotherapy for the treatment of PDAC. Considered in this unit is the value of genetic mouse models for characterizing the immunobiology of PDAC and for investigating novel immunotherapeutics. Several variants of these models are described, all of which may be used in drug development and for providing information on unique aspects of disease biology and therapeutic responsiveness. © 2016 by John Wiley & Sons, Inc.

Keywords: genetically engineered mouse model; immunotherapy; inflammation; KPC; macrophage; pancreatic ductal adenocarcinoma; T cell exclusion

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Table of Contents

  • Introduction
  • Genetic Mouse Models of PDAC
  • Immunobiology of Human and Mouse PDAC
  • Immuno‐Oncology Discovery Using Genetic Models of PDAC
  • The Value of Genetic Models for Evaluating Immunotherapy In PDAC
  • Application of Genetic Models of PDAC and Their Variants to Preclinical Development of Immunotherapy
  • Conclusions
  • Literature Cited
  • Figures
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Literature Cited

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