Immunotherapy with autologous tumor cells engineered to secrete Tag7/PGRP, an innate immunity recognition molecule.
BACKGROUND
Recent studies indicate that the innate component of immune defense plays an important role in the establishment of antigen-specific immune response. We have previously isolated a novel mouse gene tag7/PGRP that was shown to be involved in the innate component of the immune system, and its insect homologue is an upstream mediator of Toll signaling in Drosophila.


METHODS
Transiently or stably genetically modified mouse tumor cell lines expressing Tag7 were used. Tumor growth rate and animal survival were analyzed. Possible effector cells involved in tumor suppression were detected immunohistochemically.


RESULTS
Transfection of mammary gland adenocarcinoma cells with the tag7 cDNA did not alter their growth rate in vitro but diminished their tumorogenicity in vivo in syngeneic and immunodeficient animals. Increased incidence of apoptosis was registered in the modified tumors. Transient expression of Tag7 by mouse melanoma M3 cells elicited protective immunity against parental tumor cells. Immunohistochemical analysis revealed that tumors after immunization with the genetically modified cells were infiltrated with Mac1(+) cells, B220(+) cells, and NK cells. Using nude mice we observed rejection of modified cells, but did not detect memory formation.


CONCLUSIONS
We can conclude that secretion of the Tag7 protein by genetically modified cells can induce mobilization of antigen-presenting cells and innate effectors. Memory mechanisms are mediated by T cell response. For the first time our results demonstrate that local secretion of Tag7-the molecule involved in innate immunity-may play an important role in the induction of effective antitumor response in mice.
Larin
Sergey S
SS
Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
Korobko
Elena V
EV
Kustikova
Olga S
OS
Borodulina
Olga R
OR
Raikhlin
Natan T
NT
Brisgalov
Igor P
IP
Georgiev
Georgii P
GP
Kiselev
Sergei L
SL
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D007150:Immunohistochemistry; D007167:Immunotherapy; D051379:Mice; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; C113582:Pglyrp1 protein, mouse