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TAA/ecdCD40L adenoviral prime-protein boost vaccine for cancer and infectious diseases

Cancer Gene Therapy volume 20, pages 65–69 (2013)Cite this article

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Abstract

A vaccine platform has been created by attaching the target-associated antigen (TAA) for the vaccine to the extracellular domain (ecd) of the potent immunostimulatory signal CD40 ligand (CD40L). Attachment of the TAA to the CD40L promotes uptake of the TAA into dendritic cells (DCs), binding to Class I as well as Class II MHC leading to presentation of the TAA on the DCs, expansion of the TAA-specific B cell and CD8 effector T-cell lymphocytes, and induction of a memory response. In addition, the TAA/ecdCD40L vaccine can overcome anergy, induce regressions of pre-existing subcutaneous (SC) nodules of cancer cells, and induce high titers of neutralizing antibodies against viral antigens. This vaccine, which can be administered SC as a TAA/ecdCD40L fusion protein, or as expression vectors (viral or plasmid) or as a vector prime-protein boost strategy, is applicable to the development of vaccine for a wide range of cancers and infectious agents.

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Acknowledgements

This paper covers work performed over a lengthy period and various aspects of the work were supported by the Breast Cancer Research Foundation of New York City, the Department of Defense Breast Cancer Research Program, the NIH (SBIR), the State of California Breast Cancer Research Fund, and the Wolman Foundation.

Author contributions

Collaborators on the pre-clinical work included: YT, LZ, LP, HA, JF and NH. The authors acknowledge extensive editorial assistance from Mr Jacob Frank. The team of Dr Han Chong Toh at the NCCS, which includes John Chia, Marissa Teo, Peter Wang, TE Huat, LS Swan, Damien Lim, Poon Yee Eng, Pan Chai Pen, Tan Sze Huey, HS Wan TS Huey of the National Cancer Center of Singaore and John Connelly of the Immunology Network of A-Star of the Biopolis of Singapore, will be participating in the ongoing trial at the National Cancer Center of Singapore.

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Authors and Affiliations

  1. MicroVAX LLC, Manassas, VA, USA

    A Deisseroth, Y Tang & L Zhang

  2. University of Ankara, Ankara, Turkey

    H Akbulut

  3. Hammersmith Hospital, London, UK

    N Habib

Authors
  1. A Deisseroth
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  2. Y Tang
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  3. L Zhang
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  4. H Akbulut
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  5. N Habib
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Corresponding author

Correspondence to A Deisseroth.

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Competing interests

The following are founders of MicroVAX, LLC and VAXum, LLC, which is organizing the development of the TAA/ecdCD40L vaccine technology: Albert Deisseroth, Jacob Frank and Nagy Habib. The following are members of MicroVAX and VAXum: Albert Deisseroth, Yucheng Tang, Lixin Zhang, Jacob Frank and Nagy Habib.

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Deisseroth, A., Tang, Y., Zhang, L. et al. TAA/ecdCD40L adenoviral prime-protein boost vaccine for cancer and infectious diseases. Cancer Gene Ther 20, 65–69 (2013). https://doi.org/10.1038/cgt.2012.87

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