37 kiloDalton oncofetal antigen protein and immature laminin receptor protein are identical, universal T-cell inducing immunogens on primary rodent and human cancers.
Based upon positive immunologic comparisons, protein and cDNA sequencing, and in vitro and in vivo immunogenicity studies we propose that carcinomas, sarcomas and lymphomas/leukemias of rodents and humans share 37 kDa Onco-Fetal Antigen [OFA] as a T and B-lymphocyte stimulating, universal tumor specific transplantation antigen [UTSTA]. In the past four years, biochemical studies from several laboratories studying laminin receptor protein and immunological studies of OFA from our laboratories independently converged. OFA protein and immature or precursor Laminin Receptor Protein [iLRP] are > 99% identical proteins based on amino acid and cDNA sequencing and immunobiology studies summarized here. Acquired expression of 37 kDa OFA/iLRP enables malignant tumor cells to penetrate laminin tissue and vessel barriers. 37 kDa OFA/iLRP activates precursor thymic anti-OFA/iLRP specific cytotoxic T cell which kill emerging pretumor cells. Our reported findings also demonstrate that OFA/iLRP can function to induce specific immunoregulatory CD8 T-suppressor cells secreting IL-10 which impair effector T-cell killing of emerging tumor cells non-specifically and thereby facilitate tumor progression. Potential applications of OFA/iLRP detection in early cancer formation, for monitoring patient T cell subclass responses to OFA/iLRP as a predictor of tumor progression, and the use of OFA/iLRP peptides for specific anti-tumor immunotherapy are presented.
Coggin
J H
JH
Department of Microbiology and Immunology, University of South Alabama, College of Medicine, Mobile 36688-0002, USA.
Barsoum
A L
AL
Rohrer
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D018076:DNA, Complementary / Q000032:analysis; D005354:Fibrosarcoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry; D011498:Protein Precursors / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D017474:Receptors, Laminin; D017421:Sequence Analysis; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D010446:Peptide Fragments; D011498:Protein Precursors; D017474:Receptors, Laminin; C509834:immature laminin receptor protein, mouse; C031192:oncofetal antigens