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  • Open Access

The immunological basis of tumor therapy by targeted delivery of TNFa to tumor vessels

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Retrovirology20063 (Suppl 1) :P1

  • Published:


  • Melphalan
  • SCID Mouse
  • Fibrosarcoma
  • Tumor Vasculature
  • Complete Tumor

L19mTNFa is a fusion protein constituted by the scFv L19 specific for the oncofetal ED-B domain of fibronectin and TNFa. Treatment with L19mTNFa, in combination with melphalan, induced complete tumor regression in 83% of BALB/c mice with WEHI-164 fibrosarcoma and 33% of animals with C51 colon carcinoma. All cured mice rejected challenges with the same tumor cells and, in a very high percentage of animals, also challenges with syngeneic tumor cells of different histological origin. In adoptive immunity transfer experiments the splenocytes from C51-cured mice protected 100% of naive mice both from C51 colon carcinoma and from WEHI-164 fibrosarcoma. The splenocytes from WEHI-164-cured mice protected 100% of mice from the fibrosarcoma and 80% from the C51 colon carcinoma. Similar results were also obtained in adoptive immunity transfer experiments using severely immunodepressed SCID mice. Experiments using depleted splenocytes showed that T cells play a major role in tumor rejection. These data demonstrate that the selective targeting of mTNFa to the tumor enhances its immunostimulatory properties to the point of generating a therapeutic immune response against different histologically unrelated syngeneic tumors. These findings predicate treatment approaches for cancer patients based on the targeted delivery of TNFa to tumor vasculature.

Authors’ Affiliations

Department of Translational Oncology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese, Italy
Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland
Unit of Innovative Therapies, Istituto Giannina Gaslini, Centro Biotecnologie Avanzate, Genoa, Italy


© Balza et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd.