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A hsp70-2 mutation recognized by CTL on a human renal cell carcinoma
C Gaudin1, F Kremer, E Angevin
1Laboratoire d'Immunologie Cellulaire and Unité d'Immunothérapie, Institut Gustave-Roussy, Cedex, France.
Journal of Immunology (Baltimore, Md. : 1950)
|February 11, 1999
Summary
Researchers identified a mutated heat shock protein 70 (hsp70-2) gene in renal cell carcinoma tumors. This mutation creates a tumor-specific antigen recognized by T cells, offering potential for targeted cancer immunotherapies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumor-infiltrating lymphocytes (TILs) play a crucial role in anti-tumor immunity.
- Understanding the specific antigens recognized by TILs is key to developing effective cancer immunotherapies.
- Heat shock proteins (HSPs) are involved in cellular stress responses and can be tumor-associated antigens.
Purpose of the Study:
- To characterize a renal cell carcinoma (RCC)-specific cytotoxic T lymphocyte (CTL) clone.
- To identify the tumor antigen recognized by this CTL clone.
- To investigate the potential of mutated stress-induced proteins as targets for cancer immunotherapy.
Main Methods:
- T cell cloning from RCC tumor-infiltrating lymphocytes.
- Isolation and characterization of MHC class I-restricted CTL clones.
- Identification of tumor antigen via cDNA library co-transfection with HLA-A*0201 and subsequent T cell stimulation assays (TNF release).
- Peptide binding assays using T2 cells to assess recognition avidity.
Main Results:
- One RCC-specific CTL clone (TCRBV6J1S1) was isolated and characterized.
- The CTL clone recognized a mutated form of the hsp70-2 gene product expressed by the autologous tumor cells (RCC-7) in an HLA-A*0201-restricted manner.
- The identified antigenic peptide, a decamer with a mutation at position 8, was recognized with high avidity (half-maximal lysis at 5 x 10(-11) M) compared to the wild-type peptide (5 x 10(-8) M).
- Recognition was specific to the mutated antigen and not due to altered binding to HLA-A*0201.
Conclusions:
- A mutated hsp70-2 gene product serves as a specific antigen recognized by TILs in renal cell carcinoma.
- This mutated antigen is recognized with high avidity by CTLs, suggesting its potential as a target for adoptive T cell therapy.
- The findings support the concept of targeting mutated stress-induced proteins for cancer immunotherapy, potentially leveraging existing strategies using heat shock proteins.