PMID- 26197849
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 64
IP  - 11
DP  - 2015 Nov
TI  - Cytokine-enhanced maturation and migration to the lymph nodes of a human dying 
      melanoma cell-loaded dendritic cell vaccine.
PG  - 1393-406
LID - 10.1007/s00262-015-1743-z [doi]
AB  - Dendritic cells (DCs) are professional APCs used for the development of cancer 
      vaccines because of their ability to activate adaptive immune responses. 
      Previously, we designed the DC/Apo-Nec vaccine using human DCs loaded with dying 
      melanoma cells that primed Ag-specific cytotoxic T cells. Here, we evaluate the 
      effect of a standard pro-inflammatory cytokine cocktail (CC) and adjuvants on 
      DC/Apo-Nec maturation and migration. CC addition to the vaccine coculture allowed 
      efficient Ag uptake while attaining strong vaccine maturation with an 
      immunostimulatory profile. The use of CC not only increased CCR7 expression and 
      the vaccine chemokine responsiveness but also upregulated matrix 
      metalloproteinase-9 secretion, which regulated its invasive migration in vitro. 
      Neither IL-6 nor prostaglandin E2 had a negative effect on vaccine preparation. 
      In fact, all CC components were necessary for complete vaccine maturation. 
      Subcutaneously injected DC/Apo-Nec vaccine migrated rapidly to draining LNs in 
      nude mice, accumulating regionally after 48 h. The migrating cells of the 
      CC-matured vaccine augmented in proportion and range of distribution, an effect 
      that increased further with the topical administration of imiquimod cream. The 
      migrating proportion of human DCs was detected in draining LNs for at least 9 
      days after injection. The addition of CC during DC/Apo-Nec preparation enhanced 
      vaccine performance by improving maturation and response to LN signals and by 
      conferring a motile and invasive vaccine phenotype both in vitro and in vivo. 
      More importantly, the vaccine could be combined with different adjuvants. 
      Therefore, this DC-based vaccine design shows great potential value for clinical 
      translation.
FAU - Pizzurro, Gabriela A
AU  - Pizzurro GA
AD  - Centro de Investigaciones Oncologicas - Fundacion Cancer (FUCA), Cramer 1180, CP 
      1426, Buenos Aires, Argentina.
FAU - Tapia, Ivana J
AU  - Tapia IJ
AD  - Centro de Investigaciones Oncologicas - Fundacion Cancer (FUCA), Cramer 1180, CP 
      1426, Buenos Aires, Argentina.
FAU - Sganga, Leonardo
AU  - Sganga L
AD  - Laboratorio de Terapia Molecular y Celular, Fundacion Instituto Leloir - 
      Instituto de Investigaciones Bioquimicas de Buenos Aires, Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina.
FAU - Podhajcer, Osvaldo L
AU  - Podhajcer OL
AD  - Laboratorio de Terapia Molecular y Celular, Fundacion Instituto Leloir - 
      Instituto de Investigaciones Bioquimicas de Buenos Aires, Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina.
FAU - Mordoh, Jose
AU  - Mordoh J
AD  - Centro de Investigaciones Oncologicas - Fundacion Cancer (FUCA), Cramer 1180, CP 
      1426, Buenos Aires, Argentina.
AD  - Laboratorio de Cancerologia, Fundacion Instituto Leloir - Instituto de 
      Investigaciones Bioquimicas de Buenos Aires, Consejo Nacional de Investigaciones 
      Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina.
AD  - Instituto Alexander Fleming, Buenos Aires, Argentina.
FAU - Barrio, Maria M
AU  - Barrio MM
AD  - Centro de Investigaciones Oncologicas - Fundacion Cancer (FUCA), Cramer 1180, CP 
      1426, Buenos Aires, Argentina. barrio.marcela@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150722
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Aminoquinolines)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - P1QW714R7M (Imiquimod)
SB  - IM
MH  - Aminoquinolines/pharmacology
MH  - Animals
MH  - Cancer Vaccines/*immunology
MH  - Cell Movement
MH  - Chemotaxis
MH  - Cytokines/*physiology
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - Imiquimod
MH  - Lymph Nodes/*immunology
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Melanoma/*immunology/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Invasiveness
MH  - T-Lymphocytes/immunology
PMC - PMC11028647
OTO - NOTNLM
OT  - Cell migration
OT  - Dendritic cell vaccine
OT  - Imiquimod cream
OT  - Lymph node homing
OT  - Melanoma
OT  - Standard cytokine cocktail
COIS- The authors declare that they have no commercial or financial conflict of 
      interest.
EDAT- 2015/07/23 06:00
MHDA- 2016/02/03 06:00
PMCR- 2015/07/22
CRDT- 2015/07/23 06:00
PHST- 2014/09/01 00:00 [received]
PHST- 2015/07/11 00:00 [accepted]
PHST- 2015/07/23 06:00 [entrez]
PHST- 2015/07/23 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
PHST- 2015/07/22 00:00 [pmc-release]
AID - 10.1007/s00262-015-1743-z [pii]
AID - 1743 [pii]
AID - 10.1007/s00262-015-1743-z [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2015 Nov;64(11):1393-406. doi: 
      10.1007/s00262-015-1743-z. Epub 2015 Jul 22.