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[Cancer Research 61, 4078-4083, May 15, 2001]
© 2001 American Association for Cancer Research

Immunology

A Point Mutation in the {alpha}-Actinin-4 Gene Generates an Antigenic Peptide Recognized by Autologous Cytolytic T Lymphocytes on a Human Lung Carcinoma1

Hamid Echchakir2, Fathia Mami-Chouaib2,,3, Isabelle Vergnon, Jean-François Baurain, Vaios Karanikas, Salem Chouaib and Pierre G. Coulie

Laboratoire Cytokines et Immunologie des tumeurs Humaines, U487 Institut National de la Santé et de la Recherche Médicale, Institut Gustave Roussy, F-94805 Villejuif, Cedex, France [H. E., F. M-C., I. V., S. C.], and Université catholique de Louvain and Institute of Cellular Pathology, Cellular Genetics Unit, Brussels, Belgium B-1200 [J-F. B., V. K., P. G. C.]

We have identified an antigen recognized on a human large cell carcinoma by an autologous tumor-specific CTL clone that was derived from mononuclear cells infiltrating the primary tumor. The antigenic peptide is presented by HLA-A2 molecules and is encoded by the {alpha}-actinin-4 gene, which is expressed ubiquitously. In the tumor cells, a point mutation generates an amino-acid change that is essential for recognition by the CTLs. The mutation was not found in {alpha}-actinin-4 cDNA sequences from about 50 lung carcinoma cell lines, suggesting that it is unique to this patient. Although he did not receive chemotherapy or radiotherapy, the patient has been without evidence of tumor since the resection of the primary lesion in 1996. Using tetramers of soluble HLA-A2 molecules loaded with the mutated antigenic peptide, anti-{alpha}-actinin-4 CTLs could be derived from blood samples collected from the patient in 1998 and 2000. It is possible that these CTLs, recognizing a truly tumor-specific antigen, play a role in the clinical evolution of this lung cancer patient.




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Copyright © 2001 by the American Association for Cancer Research.