Immunotherapy of Experimental Metastases by Vaccination with Interleukin Gene-Transduced Adenocarcinoma Cells Sharing Tumor-Associated Antigens: Comparison between IL-12 and IL-2 Gene-Transduced Tumor Cell Vaccines

Monica Rodolfo, Chiara Zilocchi, Cecilia Melani, Barbara Cappetti, Ivano Arioli, Giorgio Parmiani, Mario P. Colombo

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Abstract

We have compared the therapeutic activity and characterized the antitumor response induced by IL-12 and IL-2 gene-transduced tumor cell vaccines. Mice bearing lung metastases of the BALB/c colon carcinoma C51 were treated with syngenic, histologically related, and antigenically cross-reacting irradiated IL-12 (C26/IL12) or IL-2 (C26/IL2) gene-transduced C26 tumor cells given s.c. Vaccination with C26/IL12 cells cured 40% of mice, while vaccination with C26/IL2 cells reduced the number of metastatic nodules without affecting survival. Despite this difference, similar antitumor CTL activation was shown in mice treated with C26/IL12 or C26/IL2 cells. The lytic pattern of CTL was shown to be directed to tumor-associated Ags (TAA) shared between the colon carcinomas C51, C26, and CC36 as well as with other syngenic tumors. Both treatments induced anti-TAA Abs, but only sera from mice treated with C26/IL12 contained Ab that lysed tumor cells in a C-dependent cytotoxicity assay. Early infiltration of activated T cells was found in the lungs of mice vaccinated with C26/IL12. CD4+ lymphocytes purified from the lymph nodes draining the vaccination site or from the spleen showed a higher production of IFN-γ in response to anti-CD3 mAb in C26/IL12 vaccinated mice, while a higher production of IL-4 was shown in mice vaccinated with C26/IL2 cells. These results indicate that the better therapeutic efficacy of vaccination with C26/IL12 is associated with the production of C-binding Ab, an early infiltration of the metastatic lungs by activated T lymphocytes and a predominant systemic activation of Th1 more than Th2 cells.

Original languageEnglish
Pages (from-to)5536-5542
Number of pages7
JournalJournal of Immunology
Volume157
Issue number12
Publication statusPublished - Dec 15 1996

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Cancer Vaccines
Interleukins
Neoplasm Antigens
Interleukin-12
Immunotherapy
Interleukin-2
Vaccination
Adenocarcinoma
Neoplasm Metastasis
Genes
Neoplasms
Lung
Colon
Carcinoma
T-Lymphocytes
Th2 Cells
Interleukin-4
Therapeutics
Spleen
Cell Count

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Immunotherapy of Experimental Metastases by Vaccination with Interleukin Gene-Transduced Adenocarcinoma Cells Sharing Tumor-Associated Antigens: Comparison between IL-12 and IL-2 Gene-Transduced Tumor Cell Vaccines",
abstract = "We have compared the therapeutic activity and characterized the antitumor response induced by IL-12 and IL-2 gene-transduced tumor cell vaccines. Mice bearing lung metastases of the BALB/c colon carcinoma C51 were treated with syngenic, histologically related, and antigenically cross-reacting irradiated IL-12 (C26/IL12) or IL-2 (C26/IL2) gene-transduced C26 tumor cells given s.c. Vaccination with C26/IL12 cells cured 40{\%} of mice, while vaccination with C26/IL2 cells reduced the number of metastatic nodules without affecting survival. Despite this difference, similar antitumor CTL activation was shown in mice treated with C26/IL12 or C26/IL2 cells. The lytic pattern of CTL was shown to be directed to tumor-associated Ags (TAA) shared between the colon carcinomas C51, C26, and CC36 as well as with other syngenic tumors. Both treatments induced anti-TAA Abs, but only sera from mice treated with C26/IL12 contained Ab that lysed tumor cells in a C-dependent cytotoxicity assay. Early infiltration of activated T cells was found in the lungs of mice vaccinated with C26/IL12. CD4+ lymphocytes purified from the lymph nodes draining the vaccination site or from the spleen showed a higher production of IFN-γ in response to anti-CD3 mAb in C26/IL12 vaccinated mice, while a higher production of IL-4 was shown in mice vaccinated with C26/IL2 cells. These results indicate that the better therapeutic efficacy of vaccination with C26/IL12 is associated with the production of C-binding Ab, an early infiltration of the metastatic lungs by activated T lymphocytes and a predominant systemic activation of Th1 more than Th2 cells.",
author = "Monica Rodolfo and Chiara Zilocchi and Cecilia Melani and Barbara Cappetti and Ivano Arioli and Giorgio Parmiani and Colombo, {Mario P.}",
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T1 - Immunotherapy of Experimental Metastases by Vaccination with Interleukin Gene-Transduced Adenocarcinoma Cells Sharing Tumor-Associated Antigens

T2 - Comparison between IL-12 and IL-2 Gene-Transduced Tumor Cell Vaccines

AU - Rodolfo, Monica

AU - Zilocchi, Chiara

AU - Melani, Cecilia

AU - Cappetti, Barbara

AU - Arioli, Ivano

AU - Parmiani, Giorgio

AU - Colombo, Mario P.

PY - 1996/12/15

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AB - We have compared the therapeutic activity and characterized the antitumor response induced by IL-12 and IL-2 gene-transduced tumor cell vaccines. Mice bearing lung metastases of the BALB/c colon carcinoma C51 were treated with syngenic, histologically related, and antigenically cross-reacting irradiated IL-12 (C26/IL12) or IL-2 (C26/IL2) gene-transduced C26 tumor cells given s.c. Vaccination with C26/IL12 cells cured 40% of mice, while vaccination with C26/IL2 cells reduced the number of metastatic nodules without affecting survival. Despite this difference, similar antitumor CTL activation was shown in mice treated with C26/IL12 or C26/IL2 cells. The lytic pattern of CTL was shown to be directed to tumor-associated Ags (TAA) shared between the colon carcinomas C51, C26, and CC36 as well as with other syngenic tumors. Both treatments induced anti-TAA Abs, but only sera from mice treated with C26/IL12 contained Ab that lysed tumor cells in a C-dependent cytotoxicity assay. Early infiltration of activated T cells was found in the lungs of mice vaccinated with C26/IL12. CD4+ lymphocytes purified from the lymph nodes draining the vaccination site or from the spleen showed a higher production of IFN-γ in response to anti-CD3 mAb in C26/IL12 vaccinated mice, while a higher production of IL-4 was shown in mice vaccinated with C26/IL2 cells. These results indicate that the better therapeutic efficacy of vaccination with C26/IL12 is associated with the production of C-binding Ab, an early infiltration of the metastatic lungs by activated T lymphocytes and a predominant systemic activation of Th1 more than Th2 cells.

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