Synthetic oligonucleotide expressed by a recombinant vaccinia virus elicits therapeutic CTL.
Year: 1995
Type: article
Abstract: P815A is a naturally occurring tumor rejection Ag of the methylcholanthrene-induced murine mastocytoma P815. The gene encoding the Ag P815A, designated P1A, is identical to that encoded in the normal genome of the DBA/2 mouse. A recombinant vaccinia virus (rVV) was constructed that expressed a synthetic oligonucleotide encoding the minimal determinant peptide of the tumor-associated Ag. Although the rVV recombinant expressing this mini-gene was recognized efficiently in vitro, it was an ineffective immunogen in vivo. The addition of an endoplasmic reticulum insertion signal sequence to the NH2 terminus of the minimal determinant resulted in a rVV that elicited CD8+ T cells that could lyse P815 mastocytoma cells in vitro and that were therapeutic in vivo. Recombinant viruses expressing synthetic oligonucleotide sequences preceded by the insertion signal sequences allow the expression of Ag directly into the endoplasmic reticulum, where binding to MHC class I molecules is most efficient. Vaccines based on synthetic oligonucleotides could be constructed with ease and rapidity but, most importantly, such constructs avoid the dangers associated with the expression of full length genes encoding TAA that are potentially oncogenic.
Source: The Journal of Immunology
Authors: K R Irvine, B J McCabe, S A Rosenberg, N P Restifo
Institutions: National Institutes of Health, National Cancer Institute
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1944651912