MIG (CXCL9) chemokine gene therapy combines with antibody-cytokine fusion protein to suppress growth and dissemination of murine colon carcinoma
| Autor: | J M, Ruehlmann, R, Xiang, A G, Niethammer, Y, Ba, U, Pertl, C S, Dolman, S D, Gillies, R A, Reisfeld |
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| Rok vydání: | 2001 |
| Předmět: |
Mice
Inbred BALB C Lung Neoplasms Immunotoxins Recombinant Fusion Proteins Genetic Therapy Epithelial Cell Adhesion Molecule Chemokine CXCL9 Combined Modality Therapy Mice Antigens Neoplasm COS Cells Colonic Neoplasms Animals Intercellular Signaling Peptides and Proteins Interleukin-2 Female Cell Adhesion Molecules Chemokines CXC Cell Division |
| Zdroj: | Cancer research. 61(23) |
| ISSN: | 0008-5472 |
| Popis: | The induction of a CTL response capable of eradicating disseminated tumor metastases and the establishment of a persistent tumor-protective immunity remain major goals of cancer immunotherapy. Here, we demonstrate for the first time that the combination of interleukin 2 (IL-2) targeted to the tumor microenvironment by a recombinant antibody-IL-2 fusion protein (huKS1/4-IL-2) with gene therapy by the murine chemokine MIG (CXCL9) markedly reduced s.c. tumor burden and decisively suppressed dissemination of experimental lung metastases of CT26-KSA colon carcinoma in syngeneic BALB/c mice. This combined therapy significantly prolonged the life span of these mice 3-4-fold by concurrently delivering MIG and IL-2 to the tumor site and thereby achieving chemoattraction of T cells together with their activation. The antitumor effect obtained was mediated predominantly by MHC class I antigen-restricted CD8(+) T cells with help from MHC class II antigen-restricted CD4(+) T lymphocytes. In addition, the MIG chemokine also induced angiostatic effects in the tumor vasculature. Taken together, this combination of MIG chemokine gene therapy with tumor-targeted cytokine IL-2 provides an approach for the rational design of novel cancer immunotherapy modalities. |
| Databáze: | OpenAIRE |
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