New cancer therapy by immunomanipulation: Development of immunotherapy for human melanoma as a model system

Yutaka Kawakami

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose and Methods. T cells play an important role in in vivo rejection of human melanoma. Human melanoma antigens recognized by autologous T cells were identified. These antigens are classified as tissue (melanocyte)- specific proteins, cancer-testis antigens (proteins expressed in normal testis and various cancers), tumor-specific peptides derived from mutations in tumor cells, and others. Results. A variety of mechanisms generating T cell epitopes on tumor cells were discovered. Various clinical observations, including tumor regression observed in adoptive transfer of gp 100-reactive T cells suggest that these identified melanoma peptides may function as tumor rejection antigens. Immunodominant common epitopes that could expand melanoma-reactive cytotoxic T lymphocytes (CTLs) in vitro were found in the MART-1 and gp 100 antigens. New immunization protocols - including immunization with peptides, recombinant viruses, plasmid DNAs, and dendritic cells pulsed with peptides as well as adoptive transfer of in vitro-generated CTLs by stimulation with antigenic peptides - were developed (phase I clinical trials have been performed in the Surgery Branch of the National Cancer Institute, Bethesda, MD, U.S.A.). Immunization with the gp100(209(210M)) peptide that was modified to have high HLA-A2 binding affinity, along with incomplete Freund's adjuvant and interleukin (IL)-2, resulted in a 42% response rate in patients with melanoma. Conclusion. These immunotherapies need further improvement due to the mechanisms of tumor escape from T cell responses.

Original languageEnglish
JournalCornea
Volume19
Issue number3 SUPPL. 1
DOIs
Publication statusPublished - 2000 May

Fingerprint

Human Development
Immunotherapy
Melanoma
Peptides
T-Lymphocytes
Immunization
Neoplasms
Adoptive Transfer
Testicular Neoplasms
Cytotoxic T-Lymphocytes
Antigens
Therapeutics
Tumor Escape
Melanoma-Specific Antigens
HLA-A2 Antigen
Immunodominant Epitopes
Clinical Trials, Phase I
T-Lymphocyte Epitopes
DNA Viruses
National Cancer Institute (U.S.)

Keywords

  • Dendritic cells
  • Gp 100
  • Immunotherapy
  • Melanoma
  • Tumor antigens

ASJC Scopus subject areas

  • Ophthalmology

Cite this

New cancer therapy by immunomanipulation : Development of immunotherapy for human melanoma as a model system. / Kawakami, Yutaka.

In: Cornea, Vol. 19, No. 3 SUPPL. 1, 05.2000.

Research output: Contribution to journalArticle

@article{f737c3e311a64f7083828f83186e3880,
title = "New cancer therapy by immunomanipulation: Development of immunotherapy for human melanoma as a model system",
abstract = "Purpose and Methods. T cells play an important role in in vivo rejection of human melanoma. Human melanoma antigens recognized by autologous T cells were identified. These antigens are classified as tissue (melanocyte)- specific proteins, cancer-testis antigens (proteins expressed in normal testis and various cancers), tumor-specific peptides derived from mutations in tumor cells, and others. Results. A variety of mechanisms generating T cell epitopes on tumor cells were discovered. Various clinical observations, including tumor regression observed in adoptive transfer of gp 100-reactive T cells suggest that these identified melanoma peptides may function as tumor rejection antigens. Immunodominant common epitopes that could expand melanoma-reactive cytotoxic T lymphocytes (CTLs) in vitro were found in the MART-1 and gp 100 antigens. New immunization protocols - including immunization with peptides, recombinant viruses, plasmid DNAs, and dendritic cells pulsed with peptides as well as adoptive transfer of in vitro-generated CTLs by stimulation with antigenic peptides - were developed (phase I clinical trials have been performed in the Surgery Branch of the National Cancer Institute, Bethesda, MD, U.S.A.). Immunization with the gp100(209(210M)) peptide that was modified to have high HLA-A2 binding affinity, along with incomplete Freund's adjuvant and interleukin (IL)-2, resulted in a 42{\%} response rate in patients with melanoma. Conclusion. These immunotherapies need further improvement due to the mechanisms of tumor escape from T cell responses.",
keywords = "Dendritic cells, Gp 100, Immunotherapy, Melanoma, Tumor antigens",
author = "Yutaka Kawakami",
year = "2000",
month = "5",
doi = "10.1097/00003226-200005001-00002",
language = "English",
volume = "19",
journal = "Cornea",
issn = "0277-3740",
publisher = "Lippincott Williams and Wilkins",
number = "3 SUPPL. 1",

}

TY - JOUR

T1 - New cancer therapy by immunomanipulation

T2 - Development of immunotherapy for human melanoma as a model system

AU - Kawakami, Yutaka

PY - 2000/5

Y1 - 2000/5

N2 - Purpose and Methods. T cells play an important role in in vivo rejection of human melanoma. Human melanoma antigens recognized by autologous T cells were identified. These antigens are classified as tissue (melanocyte)- specific proteins, cancer-testis antigens (proteins expressed in normal testis and various cancers), tumor-specific peptides derived from mutations in tumor cells, and others. Results. A variety of mechanisms generating T cell epitopes on tumor cells were discovered. Various clinical observations, including tumor regression observed in adoptive transfer of gp 100-reactive T cells suggest that these identified melanoma peptides may function as tumor rejection antigens. Immunodominant common epitopes that could expand melanoma-reactive cytotoxic T lymphocytes (CTLs) in vitro were found in the MART-1 and gp 100 antigens. New immunization protocols - including immunization with peptides, recombinant viruses, plasmid DNAs, and dendritic cells pulsed with peptides as well as adoptive transfer of in vitro-generated CTLs by stimulation with antigenic peptides - were developed (phase I clinical trials have been performed in the Surgery Branch of the National Cancer Institute, Bethesda, MD, U.S.A.). Immunization with the gp100(209(210M)) peptide that was modified to have high HLA-A2 binding affinity, along with incomplete Freund's adjuvant and interleukin (IL)-2, resulted in a 42% response rate in patients with melanoma. Conclusion. These immunotherapies need further improvement due to the mechanisms of tumor escape from T cell responses.

AB - Purpose and Methods. T cells play an important role in in vivo rejection of human melanoma. Human melanoma antigens recognized by autologous T cells were identified. These antigens are classified as tissue (melanocyte)- specific proteins, cancer-testis antigens (proteins expressed in normal testis and various cancers), tumor-specific peptides derived from mutations in tumor cells, and others. Results. A variety of mechanisms generating T cell epitopes on tumor cells were discovered. Various clinical observations, including tumor regression observed in adoptive transfer of gp 100-reactive T cells suggest that these identified melanoma peptides may function as tumor rejection antigens. Immunodominant common epitopes that could expand melanoma-reactive cytotoxic T lymphocytes (CTLs) in vitro were found in the MART-1 and gp 100 antigens. New immunization protocols - including immunization with peptides, recombinant viruses, plasmid DNAs, and dendritic cells pulsed with peptides as well as adoptive transfer of in vitro-generated CTLs by stimulation with antigenic peptides - were developed (phase I clinical trials have been performed in the Surgery Branch of the National Cancer Institute, Bethesda, MD, U.S.A.). Immunization with the gp100(209(210M)) peptide that was modified to have high HLA-A2 binding affinity, along with incomplete Freund's adjuvant and interleukin (IL)-2, resulted in a 42% response rate in patients with melanoma. Conclusion. These immunotherapies need further improvement due to the mechanisms of tumor escape from T cell responses.

KW - Dendritic cells

KW - Gp 100

KW - Immunotherapy

KW - Melanoma

KW - Tumor antigens

UR - http://www.scopus.com/inward/record.url?scp=0034038416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034038416&partnerID=8YFLogxK

U2 - 10.1097/00003226-200005001-00002

DO - 10.1097/00003226-200005001-00002

M3 - Article

C2 - 10832714

AN - SCOPUS:0034038416

VL - 19

JO - Cornea

JF - Cornea

SN - 0277-3740

IS - 3 SUPPL. 1

ER -