PMID- 24038990
OWN - NLM
STAT- MEDLINE
DCOM- 20140514
LR  - 20211203
IS  - 1521-2254 (Electronic)
IS  - 1099-498X (Linking)
VI  - 15
IP  - 10
DP  - 2013 Oct
TI  - Interleukin-15 gene therapy and the mammalian target of rapamycin inhibitor 
      everolimus inhibit the growth of metastatic breast cancer.
PG  - 366-74
LID - 10.1002/jgm.2739 [doi]
AB  - BACKGROUND: Novel methods to control and treat metastatic breast cancer are 
      needed. Interleukin (IL)-15 is a promising cytokine for cancer immunotherapy, and 
      everolimus is an orally administered mammalian target of rapamycin (mTOR) 
      inhibitor, which is already approved for cancer treatment. In the present study, 
      we investigated the efficacy of IL-15 gene therapy and explored the possibility 
      of combining IL-15 therapy with everolimus to treat metastatic breast cancer. 
      METHODS: A plasmid encoding IL-15 and everolimus were given to mice inoculated 
      with 4 T1 mouse breast cancer cells. Tumor size and metastasis were monitored to 
      assess the effect of different treatment regimens. Immunohistochemistry was used 
      to detect CD4(+), CD8(+) and NKG2D(+) cells and also the expression of Ki-67 in tumor 
      tissue; these analyses helped establish the immunization status and tumor 
      proliferation rate of different treatment groups. Terminal deoxynucleotidyl 
      transferase dUTP nick end labeling assays were performed to assess cellular 
      apoptosis in tumor tissues. RESULTS: Both IL-15 and everolimus significantly 
      decreased tumor size. IL-15 gene therapy increased the proportion of CD4(+) T and 
      natural killer (NK) cells but had no effect on CD8(+) T cells. By contrast, 
      everolimus decreased the number of CD8(+) T cells but had no effect on CD4(+) T and 
      NK cells compared to the control group. Both IL-15 and everolimus decreased 
      expression of Ki-67 and increased rates of apoptosis. Although effective on their 
      own, no synergistic effect was observed with a combined treatment of everolimus 
      and IL-15 gene therapy. CONCLUSIONS: IL-15 gene therapy was potentially useful 
      for the treatment of metastatic breast cancer. The possibility of combining 
      immunotherapy with everolimus requires further study.
CI  - Copyright (c) 2013 John Wiley & Sons, Ltd.
FAU - Zhao, Na
AU  - Zhao N
AD  - Department of General Surgery, Tianjin Medical University General Hospital, 
      Tianjin, China.
FAU - Li, Xiaodan
AU  - Li X
FAU - He, Xianghui
AU  - He X
FAU - Qiu, Yujie
AU  - Qiu Y
FAU - Zhu, Liwei
AU  - Zhu L
FAU - Qi, Feng
AU  - Qi F
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Interleukin-15)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/*pharmacology
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*genetics/immunology/pathology/*therapy
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Combined Modality Therapy
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Everolimus
MH  - Female
MH  - Gene Order
MH  - Genetic Therapy
MH  - Genetic Vectors/genetics
MH  - Immunotherapy
MH  - Interleukin-15/*genetics
MH  - Mice
MH  - Neoplasm Metastasis
MH  - Protein Kinase Inhibitors/administration & dosage/*pharmacology
MH  - Sirolimus/administration & dosage/*analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - Tumor Burden/drug effects/genetics
OTO - NOTNLM
OT  - breast cancer
OT  - everolimus
OT  - gene therapy
OT  - interleukin-15
EDAT- 2013/09/17 06:00
MHDA- 2014/05/16 06:00
CRDT- 2013/09/17 06:00
PHST- 2013/03/08 00:00 [received]
PHST- 2013/08/10 00:00 [revised]
PHST- 2013/08/27 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
AID - 10.1002/jgm.2739 [doi]
PST - ppublish
SO  - J Gene Med. 2013 Oct;15(10):366-74. doi: 10.1002/jgm.2739.