Enhanced inhibition of tumour growth and metastasis, and induction of antitumour immunity by IL-2-IgG2b fusion protein.
Cytokine-immunoglobulin (Ig)-fusion proteins have attracted increasing interest as antitumour agents. Here, we have investigated the antimetastatic and antitumour responses elicited in vivo by mammary adenocarcinoma cells (TS/A) engineered to secrete interleukin (IL)-2-IgG fusion proteins. TS/A cells were transfected with DNA coding for IL-2-IgG2b, IgG2b or IL-2, and injected subcutaneously into syngeneic mice. Animals injected with TS/A-IL-2 or TS/A-IL-2-IgG2b both efficiently rejected tumours, whereas treatment with parental cells or TS/A-IgG2b was lethal. Interestingly, only mice vaccinated with IL-2-IgG2b fusion protein-secreting cells showed a long-lasting protective immunity against a later challenge with parental tumour cells. Moreover, the metastatic potential of TS/A-IL-2-IgG2b-transfected cells was dramatically decreased compared with TS/A-IL-2-cells, with a virtual absence of lung metastases after intravenous injection. Adenocarcinomas secreting IL-2-IgG2b exhibited a more prominent, early and persistent infiltration of CD4+, CD8+ and natural killer (NK) cells than TS/A-IL-2 cells. Therefore, upon transfection into adenocarcinoma cells, the IgG2b part of IL-2 fusion protein exerts intriguing added antitumour properties over IL-2 alone, thus contributing to a long-lasting tumour immunity, probably by the recruitment of specific immune effector cells. These findings suggest a promising new oncotherapeutic strategy for poorly immunogenic tumours: vaccination with tumour cells engineered to secrete IL-2-IgG2b fusion protein.
Budagian
V
V
Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany.
Nanni
P
P
Lollini
P L
PL
Musiani
P
P
Di Carlo
E
E
Bulanova
E
E
Paus
R
R
Bulfone-Paus
S
S
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D007150:Immunohistochemistry; D007167:Immunotherapy; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D007074:Immunoglobulin G; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins