PMID- 21544806
OWN - NLM
STAT- MEDLINE
DCOM- 20130124
LR  - 20210105
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 129
IP  - 9
DP  - 2011 Nov 1
TI  - Humanized tumor mice--a new model to study and manipulate the immune response in 
      advanced cancer therapy.
PG  - 2194-206
LID - 10.1002/ijc.26159 [doi]
AB  - 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 IL2Rgamma(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.
CI  - Copyright (c) 2011 UICC.
FAU - Wege, Anja K
AU  - Wege AK
AD  - Institute of Immunology, University of Regensburg, Regensburg, Germany.
FAU - Ernst, Wolfgang
AU  - Ernst W
FAU - Eckl, Judith
AU  - Eckl J
FAU - Frankenberger, Bernhard
AU  - Frankenberger B
FAU - Vollmann-Zwerenz, Arabel
AU  - Vollmann-Zwerenz A
FAU - Mannel, Daniela N
AU  - Mannel DN
FAU - Ortmann, Olaf
AU  - Ortmann O
FAU - Kroemer, Alexander
AU  - Kroemer A
FAU - Brockhoff, Gero
AU  - Brockhoff G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110721
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Interleukin-15)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*immunology/*therapy
MH  - Cell Line, Tumor
MH  - *Disease Models, Animal
MH  - Female
MH  - Graft Rejection/immunology
MH  - Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Interleukin-15/immunology/pharmacology
MH  - Killer Cells, Natural/drug effects/immunology
MH  - *Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - T-Lymphocytes/immunology
EDAT- 2011/05/06 06:00
MHDA- 2013/01/25 06:00
CRDT- 2011/05/06 06:00
PHST- 2010/11/10 00:00 [received]
PHST- 2011/04/12 00:00 [accepted]
PHST- 2011/05/06 06:00 [entrez]
PHST- 2011/05/06 06:00 [pubmed]
PHST- 2013/01/25 06:00 [medline]
AID - 10.1002/ijc.26159 [doi]
PST - ppublish
SO  - Int J Cancer. 2011 Nov 1;129(9):2194-206. doi: 10.1002/ijc.26159. Epub 2011 Jul 
      21.