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  • Open Access

The human CD40 agonistic antibody ADC-1013 generates immune mediated anti-tumor effects in syngeneic tumor models in hCD40 transgenic mice

  • 1,
  • 2,
  • 1,
  • 2,
  • 2,
  • 2,
  • 3,
  • 1 and
  • 2
Journal for ImmunoTherapy of Cancer20142(Suppl 3):P251

https://doi.org/10.1186/2051-1426-2-S3-P251

Published: 6 November 2014

Keywords

  • Melanoma
  • Dendritic Cell
  • Bladder Cancer
  • Tumor Immunity
  • Tumor Challenge

Local activation of costimulatory pathways by e.g. CD40 activation has been shown to generate powerful systemic anti-tumor responses. Here we report significant anti-tumor effects obtained with an optimized fully human agonistic CD40 antibody, ADC-1013, in two syngeneic tumor models.

An hCD40 transgenic mouse (hCD40tg) strain was used to evaluate the immune mediated anti-tumor effects of ADC-1013. Dendritic cells obtained from hCD40tg mice were hCD40 positive and could be activated by stimulation with ADC-1013 to a similar extent as human monocyte derived dendritic cells. Furthermore, stimulation of dendritic cells from hCD40tg mice in vitro, with ADC-1013, induced antigen specific T cell activation.

Two different syngeneic tumor models, hCD40 negative MB49 bladder cancer and hCD40 positive B16.F10.hCD40+ melanoma, was used to demonstrate anti-tumor effects. Subcutaneous tumors from both models were characterized by flow cytometry and immunohistochemistry in hCD40tg mice. Treatment of the bladder cancer model (MB49) with ADC-1013 resulted in significant anti-tumor response and long term tumor immunity. The anti-tumor immunity was shown to be T cell dependent and naïve mice were protected from tumor challenge by transplantation of splenocytes from cured hCD40tg mice. In addition, significant anti-tumor effect was demonstrated in a subcutaneous B16.F10.hCD40+ melanoma model.

The human CD40 agonistic antibody ADC-1013 is the first costimulatory antibody optimized for local immunotherapy of cancer. Strong immune mediated anti-tumor effects were demonstrated. ADC-1013 is currently in late pre-clinical development.

Authors’ Affiliations

(1)
Immunology, Genetics and Pathology, IGP, Uppsala University, Uppsala, Sweden
(2)
Alligator Bioscience AB, Lund, Sweden
(3)
Immunotechnology, Lund University, Sweden

Copyright

© Mangsbo et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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