MURINE HOMOLOGS TO HUMAN TUMOR-ASSOCIATED ANTIGENS IDENTIFIED IN THE C3H NONIMMUNOGENIC FIBROSARCOMA TUMOR MODEL.

Abstract

SEREX was used to identify candidate tumor antigens in the nonimmunogenic fibrosarcoma (NFSA) tumor model. One of the six clones identified was of particular interest. NFSA-5 was identified as the receptor for hylaronan-acid-mediated motility (RHAMM), which is involved in cell growth and metastasis. RHAMM is expressed in a variety of human tumors. RHAMM is differentially expressed, with significant levels not found in normal tissues other than testis, placenta, and thymus. Therefore, RHAMM may be an appealing target for human tumor vaccines. The identification of murine homologs to human tumor antigens may aid in the preclinical development of human tumor vaccines.

The goal of our studies was to use serological analysis of antigens by recombinant expression cloning (SEREX) to identify candidate tumor antigens in a nonimmunogenic murine fibrosarcoma model.

SEREX provides a rapid means of identifying candidate tumor antigens in murine cancer models.

The identification of murine homologs to human tumor antigens may aid in the preclinical development of human tumor vaccines.

The SEREX approach included construction of a cDNA expression library from NFSA tumors followed by immunoscreening of the library with sera from C3H mice growing NFSA tumors. The nucleotide sequence of insert cDNA was determined for positive clones. Sequence alignments were performed with BLAST software on GenBank database.

Six positive clones were identified. Two clones coded for proteins with known expression in normal tissues. Two clones represented heat-shock proteins, known to be upregulated in human and murine tumors. Two of the clones were of particular interest. Clone NFSA-1 was the homolog to NY-REN-58, an antigen previously identified by SEREX analysis of renal cell carcinoma patients. NFSA-5 was identified as the receptor for the hylaronan-acid-mediated motility (RHAMM), which is involved in cell growth and metastasis. RHAMM was recently identified as a leukemia-associated antigen and is expressed in a variety of human solid tumors including renal cell carcinoma, breast carcinoma, and ovarian carcinoma. RHAMM is differentially expressed, with significant levels not found in normal tissues other than testis, placenta, and thymus. Therefore, RHAMM may be an appealing target for human tumor vaccines.

Funding: This study was supported by a grant received from the William E. McElroy Charitable Foundation.