PMID- 34445092
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20220128
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 16
DP  - 2021 Aug 4
TI  - Dendritic Cells Pulsed with Cytokine-Adjuvanted Tumor Membrane Vesicles Inhibit 
      Tumor Growth in HER2-Positive and Triple Negative Breast Cancer Models.
LID - 10.3390/ijms22168377 [doi]
LID - 8377
AB  - Dendritic cells (DCs) are the most effective antigen presenting cells for the 
      development of T cell responses. The only FDA approved DC-based immunotherapy to 
      date is Sipuleucel-T, which utilizes a fusion protein to stimulate DCs ex vivo 
      with GM-CSF and simultaneously deliver the antigen PAP for prostate cancer. This 
      approach is restricted by the breadth of immunity elicited to a single antigen, 
      and to cancers that have a defined tumor associated antigen. Other multi-antigen 
      approaches have been restricted by poor efficacy of vaccine adjuvants. We have 
      developed a vaccine platform that consists of autologous DCs pulsed with 
      cytokine-adjuvanted tumor membrane vesicles (TMVs) made from tumor tissue, that 
      encapsulate the antigenic landscape of individual tumors. Here we test the 
      efficacy of DCs pulsed with TMVs incorporated with glycolipid-anchored 
      immunostimulatory molecules (GPI-ISMs) in HER2-positive and triple negative 
      breast cancer murine models. Pulsing of DCs with TMVs containing GPI-ISMs results 
      in superior uptake of vesicles, DC activation and cytokine production. Adaptive 
      transfer of TMV-pulsed DCs to tumor bearing mice results in the inhibition of 
      tumor growth, reduction in lung metastasis, and an increase in immune cell 
      infiltration into the tumors. These observations suggest that DCs pulsed with 
      TMVs containing GPI-GM-CSF and GPI-IL-12 can be further developed to be used as a 
      personalized immunotherapy platform for cancer treatment.
FAU - Munoz, Luis E
AU  - Munoz LE
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, Atlanta, GA 30322, USA.
FAU - Monterroza, Lenore
AU  - Monterroza L
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, Atlanta, GA 30322, USA.
FAU - Bommireddy, Ramireddy
AU  - Bommireddy R
AUID- ORCID: 0000-0001-7367-3159
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, Atlanta, GA 30322, USA.
FAU - Shafizadeh, Yalda
AU  - Shafizadeh Y
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, Atlanta, GA 30322, USA.
FAU - Pack, Christopher D
AU  - Pack CD
AD  - Metaclipse Therapeutics Corporation, Atlanta, GA 30340, USA.
FAU - Ramachandiran, Sampath
AU  - Ramachandiran S
AD  - Metaclipse Therapeutics Corporation, Atlanta, GA 30340, USA.
FAU - Reddy, Shaker J C
AU  - Reddy SJC
AD  - Metaclipse Therapeutics Corporation, Atlanta, GA 30340, USA.
FAU - Selvaraj, Periasamy
AU  - Selvaraj P
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, Atlanta, GA 30322, USA.
AD  - Department of Pathology and Laboratory Medicine, Emory University, Woodruff 
      Memorial Building, Room 7309 101 Woodruff Circle, Atlanta, GA 30322, USA.
LA  - eng
GR  - R01 CA202763/CA/NCI NIH HHS/United States
GR  - R01CA202763/NH/NIH HHS/United States
GR  - R01CA202763-S/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20210804
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Erbb2 protein, mouse)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigens, Neoplasm/*immunology
MH  - Cancer Vaccines/immunology/therapeutic use
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Cytokines/*immunology
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Receptor, ErbB-2/analysis/*immunology
MH  - Triple Negative Breast Neoplasms/immunology/pathology/*therapy
PMC - PMC8395038
OTO - NOTNLM
OT  - GPI-GM-CSF
OT  - GPI-IL-12
OT  - HER2
OT  - breast cancer
OT  - dendritic cells
OT  - immunotherapy
OT  - vaccine
COIS- Periasamy Selvaraj holds shares in Metaclipse Therapeutics Corporation, a company 
      that is planning to use GPI-anchored molecules to develop membrane-based cancer 
      vaccine in the future as suggested in the current manuscript.
EDAT- 2021/08/28 06:00
MHDA- 2021/09/21 06:00
PMCR- 2021/08/04
CRDT- 2021/08/27 01:22
PHST- 2021/06/22 00:00 [received]
PHST- 2021/07/27 00:00 [revised]
PHST- 2021/07/29 00:00 [accepted]
PHST- 2021/08/27 01:22 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2021/08/04 00:00 [pmc-release]
AID - ijms22168377 [pii]
AID - ijms-22-08377 [pii]
AID - 10.3390/ijms22168377 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Aug 4;22(16):8377. doi: 10.3390/ijms22168377.