Kr. Irvine et al., SYNTHETIC OLIGONUCLEOTIDE EXPRESSED BY A RECOMBINANT VACCINIA VIRUS ELICITS THERAPEUTIC CTL, The Journal of immunology, 154(9), 1995, pp. 4651-4657
P815A is a naturally occurring tumor rejection Ag of the methylcholant
hrene-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 th
at expressed a synthetic oligonucleotide encoding the minimal determin
ant peptide of the tumor-associated Ag. Although the rVV recombinant e
xpressing this mini-gene was recognized efficiently in vitro, it was a
n ineffective immunogen in vivo. The addition of an endoplasmic reticu
lum insertion signal sequence to the NH2 terminus of the minimal deter
minant resulted in a rVV that elicited CD8(+) T cells that could lyse
P815 mastocytoma cells in vitro and that were therapeutic in vivo. Rec
ombinant viruses expressing synthetic oligonucleotide sequences preced
ed by the insertion signal sequences allow the expression of Ag direct
ly into the endoplasmic reticulum, where binding to MHC class I molecu
les is most efficient. Vaccines based on synthetic oligonucleotides co
uld be constructed with ease and rapidity but, most importantly, such
constructs avoid the dangers associated with the expression of full le
ngth genes encoding TAA that are potentially oncogenic.