Therapeutic effectiveness of the immunity elicited by P815 tumor cells engineered to express the B7-2 costimulatory molecule.
It is well accepted that inoculation of B7-1-transfected tumor cells into normal mice leads to tumor rejection and subsequent resistance to challenge. However, the effectiveness of B7-2-transfected tumor cells in eliciting protective antitumor immunity is less clear. Here we show that B7-2-transfected P815 tumor cells (B7-2+) are as effective as B7-1-transfected P815 tumor cells (B7-1+) in eliciting protective immunity in normal DBA/2 mice. In addition, B7-2+ cells were found to be at least as effective as B7-1+ cells retarding tumor progression when admixed with parental P815 tumor cells prior to inoculation into normal mice. Moreover, the B7-2+ cells and the B7-1+ cells were equivalent in their ability to retard tumor growth when administered peritumorally into mice bearing established (approx. 3 mm in diameter) parental P815 tumors. Finally, P815 tumor cells infected with a recombinant replication-defective adenovirus encoding the murine B7-2 gene were effective in retarding the growth of established parental P815 tumors. Thus, B7-1 and B7-2 are comparable in terms of their ability to stimulate the generation of tumor-eradicating immunity in normal mice as well as in mice bearing established parental tumors. Moreover, adenovirus vectors can be used to generate B7-2-expressing tumor cells effective in the immunotherapy of established parental tumors.
La Motte
R N
RN
Department of Biochemistry, University of Illinois at Chicago 60612, USA.
Rubin
M A
MA
Barr
E
E
Leiden
J M
JM
Bluestone
J A
JA
Mokyr
M B
MB
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D051940:B7-2 Antigen; D005260:Female; D016233:Immunotherapy, Active; D012515:Mast-Cell Sarcoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008811:Mice, Inbred DBA; D014162:Transfection
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins