A unique mucin immunoenhancing peptide with antitumor properties.
Implantation of DA-3 mammary tumor cells into BALB/c mice results in tumor growth, metastatic lesions, and death. These cells were transfected with genes encoding for either the transmembrane (DA-3/TM) or secreted (DA-3/sec) form of human mucin 1 (MUC1). Although the gene for the secreted form lacks the transmembrane and cytoplasmic domains, the 5' sequences of these mucins are identical; however, the gene for the secreted mucin isoform ends with a sequence encoding for a unique 11 amino acid peptide. The DA-3/TM or DA-3 cells transfected with the neomycin vector only (DA-3/neo) have the same in vivo growth characteristics as the parent cell line. In contrast, DA-3/sec cells fail to grow when implanted in immunocompetent BALB/c animals. DA-3/sec cells implanted in nude mice resulted in tumor development verifying the tumorigenic potential of these cells. Pre-exposure of BALB/c mice to DA-3/sec cells afforded protection against challenge with DA-3/TM or DA-3/neo mammary tumors and the unrelated tumors K7, an osteosarcoma, and RENCA, a renal cell carcinoma. Partial protection against subsequent tumor challenges was also achieved by substituting the 11 amino acid peptide found only in the secreted MUC1 isoform, for the live DA-3/sec cells. Notably, the efficacy of this peptide is not strain restricted because it also retarded the growth of Lewis lung carcinoma cells in C57 BL/6 mice. These findings reveal that a unique peptide present in the secreted MUC1 has immunoenhancing properties and may be a potential agent for use in immunotherapy.
Herbert
Lynn M
LM
Department of Microbiology & Immunology, University of Miami School of Medicine, Miami, Florida 33101, USA.
Grosso
Joseph F
JF
Dorsey
Mantley
M
Fu
Tihui
T
Keydar
Iafa
I
Cejas
Mabel A
MA
Wreschner
Daniel H
DH
Smorodinski
Nechama
N
Lopez
Diana M
DM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000494:pharmacology* / Q000502:physiology; D009374:Neoplasms, Experimental / Q000517:prevention & control; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments