This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maccalli, C. Articles by Robbins, P. F. Search for Related Content PubMed PubMed Citation Articles by Maccalli, C. Articles by Robbins, P. F.

Identification of a Colorectal Tumor-Associated Antigen (COA-1) Recognized by CD4⁺ T Lymphocytes

Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1502 [Y. F. L., M. E-G., S. A. R., P. F. R.], and Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori, Milan, Italy [C. M.]

Only a limited number of target molecules have been shown to be recognized by colon tumor-reactive T cells, limiting the options for the development of immunotherapies for patients with colon cancer. The current studies were undertaken in an attempt to generate tumor-reactive T cells that could be used to identify and characterize novel colon tumor-associated antigens. Multiple CD4⁺ T-cell clones isolated either from tumor-infiltrating lymphocytes or peripheral blood mononuclear cells that were sensitized in vitro with autologous tumor cells from a colon cancer patient, 1869, recognized autologous tumor cells in a class II HLA-DR-restricted manner. One of the peripheral blood mononuclear cell clones, clone C111, was used to screen pools of clones that were generated from an autologous colon tumor cell line cDNA library. A cDNA clone that was isolated encoded a protein that was termed colorectal tumor-associated antigen-1 (COA-1). This product was recognized in the context of the two autologous HLA-DRß1 alleles, HLA-DRß1*0402 and DRß1*1301. The nucleotide sequence of the COA-1 transcript was nearly identical to multiple expressed sequence tag sequences that encode variants of Socius, a protein that was found recently to bind to members of the Rnd family of GTPases. The COA-1 gene was expressed at relatively comparable levels in colorectal and melanoma tumor cells, EBV-infected B cells, normal B cells, and cultured fibroblast cell lines. However, the gene that was isolated from normal cell types contained a single nucleotide substitution, resulting in an amino acid change near the COOH terminus of the protein. Although the minimal epitope recognized by CD4⁺ cells was encoded by sequences that were upstream from this substitution, C111 T cells did not appear to recognize the normal gene product. Therefore, this alteration may either affect the localization or the processing of this gene product, which may at least in part be responsible for the differential recognition of tumor and normal cells.

This article has been cited by other articles:

				R. K. Swoboda, R. Somasundaram, L. Caputo, E. M. Ochoa, P. A. Gimotty, F. M. Marincola, P. Van Belle, S. Barth, D. Elder, D. Guerry, et al. Shared MHC Class II-Dependent Melanoma Ribosomal Protein L8 Identified by Phage Display Cancer Res., April 15, 2007; 67(8): 3555 - 3559. [Abstract] [Full Text] [PDF]

				R. Valenti, V. Huber, P. Filipazzi, L. Pilla, G. Sovena, A. Villa, A. Corbelli, S. Fais, G. Parmiani, and L. Rivoltini Human Tumor-Released Microvesicles Promote the Differentiation of Myeloid Cells with Transforming Growth Factor-{beta}-Mediated Suppressive Activity on T Lymphocytes. Cancer Res., September 15, 2006; 66(18): 9290 - 9298. [Abstract] [Full Text] [PDF]

				M. Sensi and A. Anichini Unique Tumor Antigens: Evidence for Immune Control of Genome Integrity and Immunogenic Targets for T Cell-Mediated Patient-Specific Immunotherapy Clin. Cancer Res., September 1, 2006; 12(17): 5023 - 5032. [Abstract] [Full Text] [PDF]