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Humanized tumor mice—A new model to study and manipulate the immune response in advanced cancer therapy
Author(s) -
Wege Anja K.,
Ernst Wolfgang,
Eckl Judith,
Frankenberger Bernhard,
VollmannZwerenz Arabel,
Männel Daniela N.,
Ortmann Olaf,
Kroemer Alexander,
Brockhoff Gero
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26159
Subject(s) - immune system , humanized mouse , cancer research , cancer , immunology , biology , adoptive cell transfer , t cell , transplantation , stem cell , medicine , microbiology and biotechnology , genetics
Abstract The immunological impact on antibody‐based anticancer therapies remains incompletely understood due to the lack of appropriate animal models for in vivo analysis. Here, we present a novel humanized tumor mouse (HTM) model, generated by concurrent transplantation of human hematopoietic stem cells (HSCs) and human breast cancer cells in neonatal NOD‐ scid IL2Rγ null mice. Five weeks after intrahepatic transplantation, a functional human immune system was developed in all organs, and, in addition, tumor cells were detectable in lung and bone marrow (early dissemination). After 3 months posttransplant, tumor‐cell effusions and macroscopic tumors associated with liver or spleen were found. Furthermore, disseminated cells in different lymphoid and nonlymphoid organs were measurable. Tumor growth was accompanied by specific T‐cell maturation and tumor cell‐specific T‐cell activation. In addition, Natural–Killer cell accumulation and activation were observed in HTM, which was further enhanced upon IL‐15 treatment facilitating the possibility of immune cell modulation in, e.g. , antibody‐dependent cellular cytotoxicity‐based immunotherapeutic approaches. This novel mouse model makes it possible to combine transfer of MHC mismatched tumor cells together with human HSCs resulting in a solid coexistence and interaction without evidence for rejection. Overall, humanized tumor mice represent a powerful in vivo model that for the first time permits the investigation of human immune system‐related target cancer therapy and resistance.