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Modification of Cancer Vaccines by Virus Infection and Attachment of Bispecific Antibodies

An Effective Alternative to Somatic Gene Therapy

  • Chapter
Gene Therapy of Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 451))

Abstract

A new type of cancer vaccine for therapeutic application in cancer patients is described. It consists of three components: 1) Autologous tumor cells, 2) Newcastle Disease Virus to be used for infection and 3) bispecific antibodies (bsAb) which attach to the viral hemagglutinin neuraminidase (HN) molecule on the infected tumor cells. A standardized procedure has been developed for generating virus infected human autologous tumor cell vaccines (ATV-NDV) which includes cell dissociation removal of leukocytes and cell debris, γ-irradiation and cryopreservation. Modification with the non-virulent strain NDV-Ulster is performed within 30 minutes of co-incubation.

Virus infection potentiated tumor vaccine T cell stimulatory capacity and created a vaccine which has been successful in mouse tumor models in preventing or delaying metastatic spread and improving survival. Virus potentiation required cell surface binding but not infection. Clinical phase II studies in patients with breast or ovarian cancer suggest clinical effectivity of postoperative vaccination with a high quality ATV-NDV vaccine. Tumor cell number and viability turned out to be statistically significant parameters for quality and efficacy.

While virus infection already increased immunogenicity of the tumor vaccine, further augmentation of T cell stimulatory capacity is achieved by attachment of specially designed bispecific antibodies bsAb HN x CD28 or bsAb HN x CD3. In human T cell stimulation studies in vitro, the bsAb-vaccine caused upregulation of early and late T cell activation markers, stimulated T cell proliferation and induced cell mediated cytotoxicity and tumor cytostasis in non-modified bystander tumor cells. This tumor vaccine modification procedure is highly specific, quick and economic and has broad range clinical applications.

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Authors and Affiliations

  1. Division of Cellular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany

    Volker Schirrmacher & Claudia Haas

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  1. Volker Schirrmacher
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  2. Claudia Haas
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Editors and Affiliations

  1. Humboldt University, Berlin, Germany

    Peter Walden , Uwe Trefzer , Wolfram Sterry  & Patricia Zambon , ,  & 

  2. King’s College School of Medicine and Dentistry, London, UK

    Farzin Farzaneh

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Schirrmacher, V., Haas, C. (1998). Modification of Cancer Vaccines by Virus Infection and Attachment of Bispecific Antibodies. In: Walden, P., Trefzer, U., Sterry, W., Farzaneh, F., Zambon, P. (eds) Gene Therapy of Cancer. Advances in Experimental Medicine and Biology, vol 451. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5357-1_41

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  • DOI: https://doi.org/10.1007/978-1-4615-5357-1_41

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7444-2

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