PMID- 29543704
OWN - NLM
STAT- MEDLINE
DCOM- 20190201
LR  - 20211124
IS  - 1473-5636 (Electronic)
IS  - 0960-8931 (Print)
IS  - 0960-8931 (Linking)
VI  - 28
IP  - 3
DP  - 2018 Jun
TI  - Three antigen-loading methods in dendritic cell vaccines for metastatic melanoma.
PG  - 211-221
LID - 10.1097/CMR.0000000000000441 [doi]
AB  - In the current era of checkpoint inhibitors, some patients with metastatic 
      melanoma have shown a significant improvement in survival. However, optimization 
      of immunotherapy is an ongoing effort. Monocyte-derived dendritic cell (MODC) 
      vaccines have been shown in clinical trials to be safe and capable of inducing 
      tumor-specific immunity as well as occasional objective clinical responses. Here, 
      we conducted a three-arm pilot clinical study in 15 patients with metastatic 
      melanoma to evaluate three types of MODC vaccines, differing only by strategies 
      of tumor antigen delivery. MODCs were isolated from each patient and loaded with 
      patients' own melanoma cells as sources of antigens. Antigen loading was achieved 
      ex vivo by fusing melanoma cells with MODCs, co-culturing melanoma cells with 
      MODCs, or by pulsing MODCs with melanoma cell lysates. The vaccines were then 
      injected into superficial lymph nodes using high-resolution ultrasound guidance. 
      Primary end points included delayed-type hypersensitivity responses and positive 
      ELISpot result, which measures interferon-gamma production. Five of 15 patients 
      achieved delayed-type hypersensitivity responses and six of 15 patients had 
      positive ELISpot results. We demonstrated that the vaccines were safe and 
      well-tolerated by all patients and produced immunological responses in all arms. 
      Although MODC vaccine monotherapy has limited efficacy, combining this vaccine 
      with other immunotherapies, such as checkpoint inhibitors, to engage multiple 
      components of the immune system may be an effective and viable future approach.
FAU - Geskin, Larisa J
AU  - Geskin LJ
AD  - Department of Dermatology, Columbia University Medical Center, New York City, New 
      York.
FAU - Damiano, James J
AU  - Damiano JJ
AD  - Department of Dermatology, Columbia University Medical Center, New York City, New 
      York.
FAU - Patrone, Christina C
AU  - Patrone CC
AD  - Department of Dermatology, Columbia University Medical Center, New York City, New 
      York.
FAU - Butterfield, Lisa H
AU  - Butterfield LH
AD  - Department of Medicine, Surgery, and Immunology, University of Pittsburgh Cancer 
      Institute.
FAU - Kirkwood, John M
AU  - Kirkwood JM
AD  - Department of Medicine, University of Pittsburgh Medical Center.
FAU - Falo, Louis D
AU  - Falo LD
AD  - Department of Dermatology, University of Pittsburgh School of Medicine, 
      Pittsburgh, Pennsylvania, USA.
LA  - eng
GR  - P01 CA073743/CA/NCI NIH HHS/United States
GR  - P50 CA121973/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Melanoma Res
JT  - Melanoma research
JID - 9109623
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigens, Neoplasm/*administration & dosage/immunology
MH  - Cancer Vaccines/*therapeutic use
MH  - Dendritic Cells/*immunology/*transplantation
MH  - Female
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Male
MH  - Melanoma/immunology/pathology/*therapy
MH  - Middle Aged
MH  - Pilot Projects
MH  - Skin Neoplasms/immunology/pathology/*therapy
MH  - Survival Analysis
PMC - PMC8609477
MID - NIHMS945050
EDAT- 2018/03/16 06:00
MHDA- 2019/02/02 06:00
PMCR- 2021/11/23
CRDT- 2018/03/16 06:00
PHST- 2018/03/16 06:00 [pubmed]
PHST- 2019/02/02 06:00 [medline]
PHST- 2018/03/16 06:00 [entrez]
PHST- 2021/11/23 00:00 [pmc-release]
AID - 10.1097/CMR.0000000000000441 [doi]
PST - ppublish
SO  - Melanoma Res. 2018 Jun;28(3):211-221. doi: 10.1097/CMR.0000000000000441.