PMID- 21285988
OWN - NLM
STAT- MEDLINE
DCOM- 20110502
LR  - 20211203
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 104
IP  - 4
DP  - 2011 Feb 15
TI  - Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock 
      protein cancer vaccines.
PG  - 643-52
LID - 10.1038/bjc.2011.15 [doi]
AB  - BACKGROUND: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor and 
      rapamycin analogue that is approved for treating advanced renal cell carcinoma 
      (RCC). It is being actively evaluated in clinical trials for melanoma. The mTOR 
      inhibitors are also immunosuppressants and are used clinically to prevent 
      rejection following solid-organ transplant. Novel immunotherapies are being 
      actively developed for immunoresponsive tumours, such as RCC and melanoma. 
      METHODS: Immune-modulating effects of temsirolimus were characterised when used 
      in combination with cancer vaccines targeting RCC (RENCA) and melanoma (B16). 
      Cancer vaccines were recombinant tumour-specific proteins (CA9 or gp100), and 
      recombinant heat shock protein (HSP; hsp110) served as the immune adjuvant. 
      RESULTS: In murine models, temsirolimus enhanced the anti-tumour activity of 
      cancer vaccines used to treat established RENCA and B16 tumours. A tumour 
      prevention model established that the enhanced anti-tumour activity associated 
      with temsirolimus was immune mediated. In mice treated with an HSP-based 
      anti-tumour vaccine, temsirolimus-treated CD8 T cells had greater interferon-gamma 
      and cytotoxic T-cell responses when compared with mice treated with vaccine 
      alone. Temsirolimus also enhanced the formation of CD8 memory cells following 
      administration of HSP-based cancer vaccine. CONCLUSION: These results provide a 
      rationale for combining mTOR inhibitor with immunotherapy when treating 
      immunoresponsive tumours.
FAU - Wang, Y
AU  - Wang Y
AD  - Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, 8635 
      West 3rd Street, Suite 1070W, Los Angeles, CA 90048, USA.
FAU - Wang, X-Y
AU  - Wang XY
FAU - Subjeck, J R
AU  - Subjeck JR
FAU - Shrikant, P A
AU  - Shrikant PA
FAU - Kim, H L
AU  - Kim HL
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110201
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 624KN6GM2T (temsirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/pharmacology
MH  - Cancer Vaccines/administration & dosage/*therapeutic use
MH  - Carcinoma, Renal Cell/immunology/pathology/*therapy
MH  - Cells, Cultured
MH  - Drug Synergism
MH  - Heat-Shock Proteins/*antagonists & inhibitors/immunology
MH  - Immunosuppressive Agents/administration & dosage/therapeutic use
MH  - Immunotherapy/methods
MH  - Kidney Neoplasms/immunology/pathology/*therapy
MH  - Melanoma, Experimental/immunology/pathology/*therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Protein Kinase Inhibitors/administration & dosage/pharmacology
MH  - Sirolimus/administration & dosage/*analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
PMC - PMC3049595
COIS- The authors declared no conflict of interest.
EDAT- 2011/02/03 06:00
MHDA- 2011/05/03 06:00
PMCR- 2012/02/15
CRDT- 2011/02/03 06:00
PHST- 2011/02/03 06:00 [entrez]
PHST- 2011/02/03 06:00 [pubmed]
PHST- 2011/05/03 06:00 [medline]
PHST- 2012/02/15 00:00 [pmc-release]
AID - bjc201115 [pii]
AID - 10.1038/bjc.2011.15 [doi]
PST - ppublish
SO  - Br J Cancer. 2011 Feb 15;104(4):643-52. doi: 10.1038/bjc.2011.15. Epub 2011 Feb 
      1.