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MINERVA BIOTECNOLOGICA

Rivista di Biologia Molecolare e Biotecnologie


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  MONOCLONAL ANTIBODIES FOR IN VIVO APPLICATIONS - PART I


Minerva Biotecnologica 1998 September;10(3):89-99

lingua: Inglese

Tumor targeting with immunocytokines. A novel approach for cancer therapy

Pertl U. 1, Xiang R. 1, Kleindienst P. 2, Becker J. C. 3, Gillies S. D. 4, Reisfeld R. A. 1, Lode H. N.

1 Scripps Research Institute, Department of Immunology, La Jolla, CA, USA;
2 Institut fur Immunbiologie, Albert-Ludwing-Universitat, Freiburg, Germany;
3 Universitats Hautklinik, Wurzburg, Germany
4 Lexigen Pharmaceuticals Corp., Lexington, MA, USA


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The induction of cellular immune response capable of eradication of tumor metastases is a major goal in immunotherapy of cancer. recombinant antibody-cytokine fusion proteins are immunocytokines that effectively stimulate cellular immune responses against malignancies following an increase in cytokine concentration in the tumor microenvironment. Eradication of established pulmonary and hepatic metastases of murine melanoma and colon carcinoma in syngeneic mouse models was achieved by the activation and expansion of immune effector cells such as CD8+ T-cells by interleukin-2 immunocytokines. This effect was followed by the induction of a persistent tumor protective immunity mediated by CD8+ memory T-cells. These immunocytokines were equally effective in eliminating established bone marrow and liver metastases of murine neuroblastoma by activating natural killer (NK) cells. The effective eradication of metastases by immunocytokines resulted in significant prolongation in life span over that of controls receiving equivalent mixtures of antibody and interleukin-2 that failed to reduce the growth of disseminated metastases. Proof of concept was established indicating that immunocytokine induced activation and expansion of immune effector cells in the tumor microenvironment can effectively eradicate established tumor metastases. This promising new approach to cancer immunotherapy may lead to clinical applications that improve treatment of cancer patients with minimal residual disease in an adjuvant setting.

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