Laboratory Mice - A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma. Front Immunol 2021;12:667054
Date
06/22/2021Pubmed ID
34149703Pubmed Central ID
PMC8206561DOI
10.3389/fimmu.2021.667054Scopus ID
2-s2.0-85108140164 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
Mouse models of human cancer provide an important research tool for elucidating the natural history of neoplastic growth and developing new treatment and prevention approaches. This is particularly true for multiple myeloma (MM), a common and largely incurable neoplasm of post-germinal center, immunoglobulin-producing B lymphocytes, called plasma cells, that reside in the hematopoietic bone marrow (BM) and cause osteolytic lesions and kidney failure among other forms of end-organ damage. The most widely used mouse models used to aid drug and immunotherapy development rely on in vivo propagation of human myeloma cells in immunodeficient hosts (xenografting) or myeloma-like mouse plasma cells in immunocompetent hosts (autografting). Both strategies have made and continue to make valuable contributions to preclinical myeloma, including immune research, yet are ill-suited for studies on tumor development (oncogenesis). Genetically engineered mouse models (GEMMs), such as the widely known Vκ*MYC, may overcome this shortcoming because plasma cell tumors (PCTs) develop de novo (spontaneously) in a highly predictable fashion and accurately recapitulate many hallmarks of human myeloma. Moreover, PCTs arise in an intact organism able to mount a complete innate and adaptive immune response and tumor development reproduces the natural course of human myelomagenesis, beginning with monoclonal gammopathy of undetermined significance (MGUS), progressing to smoldering myeloma (SMM), and eventually transitioning to frank neoplasia. Here we review the utility of transplantation-based and transgenic mouse models of human MM for research on immunopathology and -therapy of plasma cell malignancies, discuss strengths and weaknesses of different experimental approaches, and outline opportunities for closing knowledge gaps, improving the outcome of patients with myeloma, and working towards a cure.
Author List
Pisano M, Cheng Y, Sun F, Dhakal B, D'Souza A, Chhabra S, Knight JM, Rao S, Zhan F, Hari P, Janz SAuthors
Anita D'Souza MD Professor in the Medicine department at Medical College of WisconsinBinod Dhakal MD Associate Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin
Jennifer M. Knight MD, MS Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Fumou Sun PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsDisease Progression
Humans
Immunotherapy
Mice
Monoclonal Gammopathy of Undetermined Significance
Multiple Myeloma
