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Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial

Metastatic and chemoresistant melanoma can be a good target of immunotherapy because it is an intractable cancer with a very poor prognosis. Previously, we tested a dendritic cell (DC)-based phase I vaccine, and confirmed that it was safe. In the present study, we performed a phase II trial of a DC...

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Autores principales: OSHITA, CHIE, TAKIKAWA, MASAKO, KUME, AKIKO, MIYATA, HARUO, ASHIZAWA, TADASHI, IIZUKA, AKIRA, KIYOHARA, YOSHIO, YOSHIKAWA, SHUSUKE, TANOSAKI, RYUJI, YAMAZAKI, NAOYA, YAMAMOTO, AKIFUMI, TAKESAKO, KAZUTOH, YAMAGUCHI, KEN, AKIYAMA, YASUTO
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583475/
https://www.ncbi.nlm.nih.gov/pubmed/22895835
http://dx.doi.org/10.3892/or.2012.1956
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author OSHITA, CHIE
TAKIKAWA, MASAKO
KUME, AKIKO
MIYATA, HARUO
ASHIZAWA, TADASHI
IIZUKA, AKIRA
KIYOHARA, YOSHIO
YOSHIKAWA, SHUSUKE
TANOSAKI, RYUJI
YAMAZAKI, NAOYA
YAMAMOTO, AKIFUMI
TAKESAKO, KAZUTOH
YAMAGUCHI, KEN
AKIYAMA, YASUTO
author_facet OSHITA, CHIE
TAKIKAWA, MASAKO
KUME, AKIKO
MIYATA, HARUO
ASHIZAWA, TADASHI
IIZUKA, AKIRA
KIYOHARA, YOSHIO
YOSHIKAWA, SHUSUKE
TANOSAKI, RYUJI
YAMAZAKI, NAOYA
YAMAMOTO, AKIFUMI
TAKESAKO, KAZUTOH
YAMAGUCHI, KEN
AKIYAMA, YASUTO
author_sort OSHITA, CHIE
collection PubMed
description Metastatic and chemoresistant melanoma can be a good target of immunotherapy because it is an intractable cancer with a very poor prognosis. Previously, we tested a dendritic cell (DC)-based phase I vaccine, and confirmed that it was safe. In the present study, we performed a phase II trial of a DC vaccine for metastatic melanoma patients with mainly the HLA-A24 genotype, and investigated the efficacy of the vaccine. Twenty-four patients with metastatic melanoma were enrolled into a phase II study of DC-based immunotherapy. The group included 19 HLA-A24-positive (A(*)2402) patients and 3 HLA-A2-positive (A(*)0201) patients. The protocol for DC production was similar to that in the phase I trial. Briefly, a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-A2, MAGE-A3 and MART-1 or MAGE-A1) restricted to HLA-A2 or A24 and KLH were used for DC pulsing. Finally, DCs were injected subcutaneously (s.c.) into the inguinal region in the dose range of 1–5×10(7) per shot. The DC ratio (lin-HLA-DR(+)) of the vaccine was 38.1±13.3% and the frequency of CD83(+) DCs was 25.7±20.8%. Other parameters regarding DC processing were not different from phase I. Immune response-related parameters including the ELISPOT assay, DTH reaction to peptide or KLH, DC injection numbers were shown to be related to a good prognosis. The ELISPOT reaction was positive in 75% of the patients vaccinated. The increase of anti-melanoma antigen antibody titer before vaccination was also shown to be a prognosis factor, but that post-vaccination was not. Based on immunohistochemical analysis, CD8 and IL-17 were not involved in the prognosis. Adverse effects of more than grade III were not seen. Overall survival analysis revealed a significant survival prolongation effect in DC-given melanoma patients. These results suggest that peptide cocktail-treated DC vaccines may be a safe and effective therapy against metastatic melanoma in terms of prolongation of overall survival time.
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spelling pubmed-35834752013-02-28 Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial OSHITA, CHIE TAKIKAWA, MASAKO KUME, AKIKO MIYATA, HARUO ASHIZAWA, TADASHI IIZUKA, AKIRA KIYOHARA, YOSHIO YOSHIKAWA, SHUSUKE TANOSAKI, RYUJI YAMAZAKI, NAOYA YAMAMOTO, AKIFUMI TAKESAKO, KAZUTOH YAMAGUCHI, KEN AKIYAMA, YASUTO Oncol Rep Articles Metastatic and chemoresistant melanoma can be a good target of immunotherapy because it is an intractable cancer with a very poor prognosis. Previously, we tested a dendritic cell (DC)-based phase I vaccine, and confirmed that it was safe. In the present study, we performed a phase II trial of a DC vaccine for metastatic melanoma patients with mainly the HLA-A24 genotype, and investigated the efficacy of the vaccine. Twenty-four patients with metastatic melanoma were enrolled into a phase II study of DC-based immunotherapy. The group included 19 HLA-A24-positive (A(*)2402) patients and 3 HLA-A2-positive (A(*)0201) patients. The protocol for DC production was similar to that in the phase I trial. Briefly, a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-A2, MAGE-A3 and MART-1 or MAGE-A1) restricted to HLA-A2 or A24 and KLH were used for DC pulsing. Finally, DCs were injected subcutaneously (s.c.) into the inguinal region in the dose range of 1–5×10(7) per shot. The DC ratio (lin-HLA-DR(+)) of the vaccine was 38.1±13.3% and the frequency of CD83(+) DCs was 25.7±20.8%. Other parameters regarding DC processing were not different from phase I. Immune response-related parameters including the ELISPOT assay, DTH reaction to peptide or KLH, DC injection numbers were shown to be related to a good prognosis. The ELISPOT reaction was positive in 75% of the patients vaccinated. The increase of anti-melanoma antigen antibody titer before vaccination was also shown to be a prognosis factor, but that post-vaccination was not. Based on immunohistochemical analysis, CD8 and IL-17 were not involved in the prognosis. Adverse effects of more than grade III were not seen. Overall survival analysis revealed a significant survival prolongation effect in DC-given melanoma patients. These results suggest that peptide cocktail-treated DC vaccines may be a safe and effective therapy against metastatic melanoma in terms of prolongation of overall survival time. D.A. Spandidos 2012-10 2012-08-07 /pmc/articles/PMC3583475/ /pubmed/22895835 http://dx.doi.org/10.3892/or.2012.1956 Text en Copyright © 2012, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
OSHITA, CHIE
TAKIKAWA, MASAKO
KUME, AKIKO
MIYATA, HARUO
ASHIZAWA, TADASHI
IIZUKA, AKIRA
KIYOHARA, YOSHIO
YOSHIKAWA, SHUSUKE
TANOSAKI, RYUJI
YAMAZAKI, NAOYA
YAMAMOTO, AKIFUMI
TAKESAKO, KAZUTOH
YAMAGUCHI, KEN
AKIYAMA, YASUTO
Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial
title Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial
title_full Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial
title_fullStr Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial
title_full_unstemmed Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial
title_short Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial
title_sort dendritic cell-based vaccination in metastatic melanoma patients: phase ii clinical trial
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583475/
https://www.ncbi.nlm.nih.gov/pubmed/22895835
http://dx.doi.org/10.3892/or.2012.1956
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