Therapy of lung metastases through combined vaccination with carcinoma cells engineered to release IL-13 and IFN-gamma.
TS/A spontaneous mouse mammary adenocarcinoma cells were engineered to release interferon-gamma (IFN-gamma), a Th1 cytokine (TS/A-IFNgamma) and interleukin-13 (IL-13), a Th2 cytokine (TS/A-IL13). Mice bearing lung micrometastases induced by parental TS/A cells received repeated subcutaneous vaccinations with TS/A-IFN-gamma admixed with TS/A-IL13 engineered cells. This combined treatment cured up to 75% of mice, whereas vaccinations with either TS/A-IFNgamma or TS/A-IL13 alone cured only 20-40% of mice. Combined TS/A-IL13 and TS/A-IFNgamma therapeutic vaccinations elicited a reactive infiltrate of CD4+ and CD8+ lymphocytes in lung metastases and an increased production of IFN-gamma in the spleen and lung, suggesting a shift of the immune response toward the Th1 type. The type of infiltrating cells along with the lack of efficacy in T cell-deficient mice point to a major role of T cells. In conclusion, no antagonism but a synergistic and effective definitive cure stems from the combined vaccination with tumor cells engineered to release a Th1 and a Th2 cytokine.
De Giovanni
C
C
Department of Experimental Pathology, University of Bologna, Italy.
Nicoletti
G
G
Landuzzi
L
L
Rossi
I
I
Astolfi
A
A
Ricci
C
C
Di Carlo
E
E
Musiani
P
P
Forni
G
G
Fradelizi
D
D
Nanni
P
P
Lollini
P L
PL
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary* / Q000628:therapy; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023421:Models, Animal
D019496:Cancer Vaccines; D016207:Cytokines; D018793:Interleukin-13; D007371:Interferon-gamma