Pre-clinical development of an agonistic CD40 antibody (ADC-1013) for local immunotherapy of cancer
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1
Alligator Bioscience, Sweden
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2
Lund University, Department of Immunotechnology, Sweden
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3
Uppsala University, Institution for Immunology, Genetics and Pathology, Sweden
Local administration of immune activating antibodies may increase the efficacy and reduce the immune-related adverse events associated with systemic immunotherapy of cancer. Here we report the development of a fully human agonistic CD40 antibody, ADC-1013, which has been optimized for local immunotherapy by FIND® recombination, thereby increasing potency and tumor retention.
ADC-1013 activates CD40 receptors on antigen-presenting cells such as dendritic cells, resulting in up-regulation of the co-stimulatory molecules CD80 and CD86, and induction of IL-12. In addition, ADC-1013 induces direct tumor killing of CD40+ tumors. The anti-tumor effects of ADC-1013 have been assessed in a bladder cancer model (EJ) in immunodeficient NSG mice. Significant anti-tumor responses were demonstrated, and further augmented in mice repopulated with human monocyte-derived dendritic cells and T cells.
To our knowledge, ADC-1013 represents the first immunomodulatory antibody optimized for local immunotherapy of cancer. It is currently in late pre-clinical development and will enter clinical trials in 2014.
Keywords:
Cancer,
Immunotherapy,
CD40,
tumor immunity,
Antigen-Presenting Cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Dahlén
E,
Furebring
C,
Broos
S,
Berggård
T,
Norlén
P,
Lindstedt
M,
Tötterman
T,
Mangsbo
S and
Ellmark
P
(2013). Pre-clinical development of an agonistic CD40 antibody (ADC-1013) for local immunotherapy of cancer.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01113
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Received:
15 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Eva Dahlén, Alligator Bioscience, Lund, Sweden, evd@alligatorbioscience.com