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PMID: 7519125 Published · ppublish English Comparative Study Journal Article

Generation of specific anti-melanoma reactivity by stimulation of human tumor-infiltrating lymphocytes with MAGE-1 synthetic peptide.

Cancer immunology, immunotherapy : CII ·Vol. 39 ·No. 2 ·1994-08-00 ·Pages 105-16

Salgaller ML, Weber JS, Koenig S, Yannelli JR, Rosenberg SA

Abstract

The MAGE-1 gene encodes a tumor-specific antigen, MZ2-E, which is recognized by cloned, specific cytolytic T cells (CTL) derived from the peripheral blood of a patient with melanoma. We have produced a MAGE-1-specific CTL line derived from the tumor-infiltrating lymphocytes (TIL) of a melanoma patient by weekly restimulation with autologous EBV-B cells pulsed with the synthetic HLA-A1-restricted MAGE-1 epitope nonapeptide EADPTGHSY. The 1277.A TIL line grew in long-term culture in low-dose interleukin-2 (IL-2) and IL-4, and exhibited antigen-specific, MHC-class-I-restricted lysis of HLA-A1-bearing MAGE-1+ cell lines. Cytolysis of target cells pulsed with the synthetic MAGE-1 decapeptide KEADPTGHSY was superior to that of cells pulsed with the immunodominant nonapeptide. Single amino-acid or even side-chain substitutions in the immunodominant nonamer abrogated cytolysis. 1277.A TIL specifically secreted tumor necrosis factor alpha after co-incubation with HLA-A1-expressing MAGE-1+ cell lines or fresh tumor. These data suggest that tumor-antigen-specific, MHC-restricted CTL may be grown from TIL in the presence of synthetic epitope peptides and expanded for adoptive immunotherapy in melanoma patients.

Related Genes
MeSH Terms
Amino Acid Sequence Antigens, Neoplasm/genetics,immunology,pharmacology B-Lymphocytes/immunology Base Sequence Cell Division/physiology Cell Transformation, Viral Cytokines/metabolism Cytotoxicity, Immunologic Epitopes Gene Expression HLA-A1 Antigen Herpesvirus 4, Human Humans Immunotherapy, Adoptive Interleukin-2/pharmacology Interleukin-4/pharmacology Lymphocyte Activation/drug effects Lymphocytes, Tumor-Infiltrating/cytology,drug effects,immunology Melanoma/blood,genetics,immunology Melanoma-Specific Antigens Molecular Sequence Data Neoplasm Proteins RNA, Neoplasm/analysis Sensitivity and Specificity Stimulation, Chemical T-Lymphocytes, Cytotoxic/cytology,drug effects,immunology
Chemicals
Antigens, Neoplasm Cytokines Epitopes HLA-A1 Antigen Interleukin-2 MAGEA1 protein, human Melanoma-Specific Antigens Neoplasm Proteins RNA, Neoplasm Interleukin-4
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Salgaller M L
Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892.
Weber J S
Koenig S
Yannelli J R
Rosenberg S A
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Article Info
Journal
Cancer immunology, immunotherapy : CII
Abbr.
Cancer Immunol Immunother
ISSN
0340-7004
Published
1994-08-00
Pages
105-16
Language
English
Region
Germany
NLM ID
8605732
Subset
IM
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