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Enhanced inhibition of tumour growth and metastasis, and induction of antitumour immunity by IL-2-IgG2b fusion protein.

Abstract：

: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.

journal_name

Scand J Immunol

journal_title

Scandinavian journal of immunology

authors

Budagian V,Nanni P,Lollini PL,Musiani P,Di Carlo E,Bulanova E,Paus R,Bulfone-Paus S

doi

10.1046/j.1365-3083.2002.01081.x

keywords:

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

484-92

issue

5

eissn

0300-9475

issn

1365-3083

pii

1081

journal_volume

55

pub_type

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