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Genes coding for tumor antigens recognized by human cytolytic T lymphocytes
P G Coulie1, P Weynants, F Lehmann
1Ludwig Institute for Cancer Research, Brussels Branch, Belgium.
Abstract:
In order to define the antigens recognized by cytolytic T lymphocytes (CTLs) on autologous tumors, we derived tumor-specific CTL clones from autologous mixed lymphocyte tumor cell cultures. The gene coding for a tumor rejection antigen expressed on a melanoma was isolated by transfecting genomic DNA of the tumor into an antigen-loss variant of the melanoma. Transfectants were identified on the basis of their ability to stimulate tumor necrosis factor release by the CTL clone. The gene that transferred the expression of the antigen was named MAGE-1. It is a new gene, silent in normal tissues with the exception of testis, but expressed in several types of tumors. The antigen recognized by the CTL clone is a nonapeptide derived from the protein encoded by gene MAGE-1, and presented by the HLA class I molecule HLA-A1. Using two other antimelanoma CTL clones, we identified the tyrosinase gene as coding for an antigen presented by HLA-A2 on this type of tumors. The identification of these tumor rejection antigens open new possibilities for the specific immunotherapy of cancer.
Insights
Researchers identified tumor rejection antigens, MAGE-1 and tyrosinase, recognized by cytolytic T lymphocytes (CTLs). This discovery advances specific cancer immunotherapy by targeting these melanoma antigens.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cytolytic T lymphocytes (CTLs) play a crucial role in recognizing and eliminating tumor cells.
- Identifying tumor-specific antigens is essential for developing effective cancer immunotherapies.
Purpose of the Study:
- To define the antigens recognized by CTLs on autologous tumors.
- To isolate genes encoding tumor rejection antigens for potential therapeutic applications.
Main Methods:
- Derived tumor-specific CTL clones from autologous mixed lymphocyte tumor cell cultures.
- Isolated melanoma rejection antigen gene (MAGE-1) by transfecting tumor DNA into an antigen-loss variant.
- Identified tyrosinase gene as another melanoma antigen using different CTL clones.
Main Results:
- Isolated the MAGE-1 gene, which encodes a tumor antigen presented by HLA-A1.
- Identified the tyrosinase gene as encoding an antigen presented by HLA-A2 on melanoma.
- MAGE-1 is a novel gene expressed in tumors but silent in most normal tissues (except testis).
Conclusions:
- The identification of MAGE-1 and tyrosinase as tumor rejection antigens opens new avenues for cancer immunotherapy.
- Targeting these specific antigens offers potential for developing personalized cancer treatments.
- This research highlights the importance of understanding antigen-MHC interactions in anti-tumor immunity.