PMID- 25168392
OWN - NLM
STAT- MEDLINE
DCOM- 20150723
LR  - 20160122
IS  - 2326-6074 (Electronic)
IS  - 2326-6066 (Linking)
VI  - 2
IP  - 12
DP  - 2014 Dec
TI  - Intravenous injection of MVA virus targets CD8+ lymphocytes to tumors to control 
      tumor growth upon combinatorial treatment with a TLR9 agonist.
PG  - 1163-74
LID - 10.1158/2326-6066.CIR-14-0050 [doi]
AB  - Effector T-cell access to tumor tissue is a limiting step for clinical efficacy 
      of antigen-specific T cell-based immunotherapies. Ectopic mouse tumor models, in 
      which a subcutaneously (s.c.) implanted tumor is treated with s.c. or 
      intramuscular therapeutic immunization, may not be optimal for targeting effector 
      T cells to an organ-borne tumor. We used an orthotopic renal carcinoma model to 
      evaluate the impact of injection routes on therapeutic efficacy of a Modified 
      Vaccinia virus Ankara viral vector expressing the human mucin 1 tumor-associated 
      xeno-antigen (MVA-MUC1). We show that intravenous (i.v.) administration of 
      MVA-MUC1 displayed enhanced efficacy when compared with s.c. injection. 
      Therapeutic efficacy of MVA-MUC1 was further enhanced by i.v. injection of a TLR9 
      agonist. In all cases, infiltration of tumor-bearing kidney by CD8(+) lymphocytes 
      was associated with control of tumor growth. Biodistribution experiments indicate 
      that, following i.v. injection, MVA-encoded antigens are quickly expressed in 
      visceral organs and, in particular, in splenic antigen-presenting cells, compared 
      with those following s.c. injection. This appears to result in a faster 
      generation of MUC1-specific CD8(+) T cells. Lymphocytes infiltrating 
      tumor-bearing kidneys are characterized by an effector memory phenotype and 
      express PD-1 and Tim3 immune checkpoint molecules. Therapeutic efficacy was 
      associated with a modification of the tumor microenvironment toward a Th1-type 
      immune response and recruitment of activated lymphocytes. This study supports the 
      clinical evaluation of MVA-based immunotherapies via the i.v. route.
CI  - (c)2014 American Association for Cancer Research.
FAU - Fend, Laetitia
AU  - Fend L
AD  - Transgene S.A., Illkirch-Graffenstaden, France.
FAU - Gatard-Scheikl, Tanja
AU  - Gatard-Scheikl T
AD  - Transgene S.A., Illkirch-Graffenstaden, France.
FAU - Kintz, Jacqueline
AU  - Kintz J
AD  - Transgene S.A., Illkirch-Graffenstaden, France.
FAU - Gantzer, Murielle
AU  - Gantzer M
AD  - Transgene S.A., Illkirch-Graffenstaden, France.
FAU - Schaedler, Emmanuelle
AU  - Schaedler E
AD  - Transgene S.A., Illkirch-Graffenstaden, France.
FAU - Rittner, Karola
AU  - Rittner K
AD  - Transgene S.A., Illkirch-Graffenstaden, France.
FAU - Cochin, Sandrine
AU  - Cochin S
AD  - Transgene S.A., Illkirch-Graffenstaden, France.
FAU - Fournel, Sylvie
AU  - Fournel S
AD  - Laboratoire de Conception et Application de Molecules Bioactives, Equipe de 
      Biovectorologie, UMR 7199 CNRS-Universite de Strasbourg, Faculte de Pharmacie, 
      Illkirch-Graffenstaden, France.
FAU - Preville, Xavier
AU  - Preville X
AD  - Transgene S.A., Illkirch-Graffenstaden, France. preville@transgene.fr.
LA  - eng
PT  - Journal Article
DEP - 20140828
PL  - United States
TA  - Cancer Immunol Res
JT  - Cancer immunology research
JID - 101614637
RN  - 0 (Cancer Vaccines)
RN  - 0 (Mucin-1)
RN  - 0 (Oligonucleotides)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - Cancer Vaccines/administration & dosage/*genetics/*immunology
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Genetic Vectors/administration & dosage/*genetics
MH  - Humans
MH  - Immunophenotyping
MH  - Immunotherapy
MH  - Injections, Intravenous
MH  - Lymphocytes, Tumor-Infiltrating/immunology/metabolism
MH  - Mice
MH  - Mucin-1/genetics/immunology
MH  - Neoplasms/genetics/*immunology/mortality/pathology/*therapy
MH  - Oligonucleotides/administration & dosage/pharmacology
MH  - Phenotype
MH  - Tissue Distribution
MH  - Toll-Like Receptor 9/*agonists
MH  - Tumor Burden/drug effects/immunology
MH  - Vaccinia virus/*genetics
EDAT- 2014/08/30 06:00
MHDA- 2015/07/24 06:00
CRDT- 2014/08/30 06:00
PHST- 2014/08/30 06:00 [entrez]
PHST- 2014/08/30 06:00 [pubmed]
PHST- 2015/07/24 06:00 [medline]
AID - 2326-6066.CIR-14-0050 [pii]
AID - 10.1158/2326-6066.CIR-14-0050 [doi]
PST - ppublish
SO  - Cancer Immunol Res. 2014 Dec;2(12):1163-74. doi: 10.1158/2326-6066.CIR-14-0050. 
      Epub 2014 Aug 28.