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

V. Budagian, P. Nanni, P. L. Lollini, P. Musiani, E. D.I. Carlo, E. Bulanova, Ralf Paus, S. Bulfone-Paus

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)484-492
Number of pages9
JournalScandinavian Journal of Immunology
Volume55
Issue number5
DOIs
StatePublished - May 8 2002
Externally publishedYes

Fingerprint

Interleukin-2
Immunity
Neoplasm Metastasis
Growth
Neoplasms
Proteins
Adenocarcinoma
Intravenous Injections
Natural Killer Cells
Antineoplastic Agents
Transfection
Immunoglobulins
Vaccination
Breast
Immunoglobulin G
Cytokines
Lung

ASJC Scopus subject areas

  • Immunology

Cite this

Budagian, V., Nanni, P., Lollini, P. L., Musiani, P., Carlo, E. D. I., Bulanova, E., ... Bulfone-Paus, S. (2002). Enhanced inhibition of tumour growth and metastasis, and induction of antitumour immunity by IL-2-IgG2b fusion protein. Scandinavian Journal of Immunology, 55(5), 484-492. https://doi.org/10.1046/j.1365-3083.2002.01081.x

Enhanced inhibition of tumour growth and metastasis, and induction of antitumour immunity by IL-2-IgG2b fusion protein. / Budagian, V.; Nanni, P.; Lollini, P. L.; Musiani, P.; Carlo, E. D.I.; Bulanova, E.; Paus, Ralf; Bulfone-Paus, S.

In: Scandinavian Journal of Immunology, Vol. 55, No. 5, 08.05.2002, p. 484-492.

Research output: Contribution to journalArticle

Budagian, V. ; Nanni, P. ; Lollini, P. L. ; Musiani, P. ; Carlo, E. D.I. ; Bulanova, E. ; Paus, Ralf ; Bulfone-Paus, S. / Enhanced inhibition of tumour growth and metastasis, and induction of antitumour immunity by IL-2-IgG2b fusion protein. In: Scandinavian Journal of Immunology. 2002 ; Vol. 55, No. 5. pp. 484-492.
@article{0117f9a299ec4fae85a50b17d24ed8fd,
title = "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.",
author = "V. Budagian and P. Nanni and Lollini, {P. L.} and P. Musiani and Carlo, {E. D.I.} and E. Bulanova and Ralf Paus and S. Bulfone-Paus",
year = "2002",
month = "5",
day = "8",
doi = "10.1046/j.1365-3083.2002.01081.x",
language = "English (US)",
volume = "55",
pages = "484--492",
journal = "Scandinavian Journal of Immunology",
issn = "0300-9475",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Enhanced inhibition of tumour growth and metastasis, and induction of antitumour immunity by IL-2-IgG2b fusion protein

AU - Budagian, V.

AU - Nanni, P.

AU - Lollini, P. L.

AU - Musiani, P.

AU - Carlo, E. D.I.

AU - Bulanova, E.

AU - Paus, Ralf

AU - Bulfone-Paus, S.

PY - 2002/5/8

Y1 - 2002/5/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0036254260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036254260&partnerID=8YFLogxK

U2 - 10.1046/j.1365-3083.2002.01081.x

DO - 10.1046/j.1365-3083.2002.01081.x

M3 - Article

VL - 55

SP - 484

EP - 492

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

SN - 0300-9475

IS - 5

ER -