Canine cancer immunotherapy studies: linking mouse and human

Jiwon S Park,Robert B Rebhun,Jaime F Modiano,William T N Culp,Mingyi Chen,Michael S Kent,Robert J Canter,William J Murphy,Jesus I Luna,Sita S Withers,Ellen E Sparger,Arta M Monjazeb

doi:10.1186/s40425-016-0200-7

Abstract

Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will...

Highlights

The ability of the immune system to recognize and eradicate transformed cells is the central rationale behind the application of immunotherapy for cancer [1]
A critical issue for the clinical translation of cancer immunotherapy is determining factors predictive of response, and unlike traditional chemotherapy or targeted therapy, key aspects of the patient’s immune milieu are likely to be as important as tumorrelated factors in determining response and toxicity
We propose that the dog model provides a critical link in pre-clinical studies since dogs are large, outbred, immunocompetent animals that develop spontaneous tumors

Summary

Introduction

The ability of the immune system to recognize and eradicate transformed cells is the central rationale behind the application of immunotherapy for cancer [1]. Recent breakthrough developments in cancer immunotherapy include checkpoint blockade therapy targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death receptor-1 (PD-1) as well as adoptive transfer of engineered T cells or chimeric antigen receptor (CAR) T cells [2,3,4,5,6,7,8,9]. A critical issue for the clinical translation of cancer immunotherapy is determining factors predictive of response, and unlike traditional chemotherapy or targeted therapy, key aspects of the patient’s immune milieu are likely to be as important as tumorrelated factors in determining response and toxicity. Data from experiments in mouse models have been invaluable to understand mechanistic concepts of immunotherapy. Intrinsic characteristics of mouse models create challenges for clinical translation. Preclinical models with intact immune systems that closely mimic the human immune system, display comparable, spontaneous oncogenesis and immune interactions to

Objectives

Findings

Conclusion