Novel Chemoattractant-Based Toxins to Improve Vaccine Immune Responses for Cancer and Infectious Diseases


Cancer is one of the leading causes of death in United States and it is estimated that there will be more than half a million deaths caused by cancer in 2009. A major drawback of the current chemotherapy-based therapeutics is the cytotoxic side-effects associated with them. Thus there is a dire need to develop new therapeutic strategies with fewer side-effects. Immunotherapy has taken a lead among the new therapeutic approaches. Enhancing the innate immune response of an individual has been a key approach for the treatment against different diseases such as cancer and infectious diseases.

This technology involves the generation of novel chemoattractant toxins that deplete the T regulatory cells (Treg) or other immunosuppressive or hyperactivated cells locally. Treg controls activation of immune responses by suppressing the induction of adaptive immune responses, particularly T cell responses. Immunosuppressive cells such as tumor infiltrating macrophages, regulatory T cells, regulatory B cells, or NKT and other cells down regulate antitumor immune responses. The chemoattractant toxins consist of a toxin moiety fused with a chemokine receptor ligand, such as chemokines and various chemoattractants, that enables specific targeting and delivery to the regulatory cells. This technology is advantageous over the more harmful antibodies and chemicals that are currently used for the systemic depletion of regulatory cells. The current technology can be used therapeutically in a variety of ways. They can be used together with vaccines to increase efficacy of the vaccine for the treatment of cancer, and can used to locally deplete Treg, Bregs, or other immuno suppressive cells to induce cytolytic cell responses at the tumor site or to eliminate chronic infectious diseases such as HIV and tuberculosis.

Potential Commercial Applications: Competitive Advantages:
  • New chemoattractant based toxins targeted towards Treg cells.
  • New chemoattractant based toxins targeted towards immunosuppressive B cells, NKT and macrophages.
  • New chemoattractant based toxins targeted towards local depletion of hyperactivated CD4 T cells to treat autoimmune diseases.
  • Chemoattractant based toxins depleting Treg cells or other immunosuppressive cells causing enhanced vaccine immune responses.
  • Novel immunotherapy by increasing vaccine efficacy against cancer and infectious diseases.
 


Development Stage:
The technology is currently in the pre-clinical stage of development.

Inventors:

Bira Arya (NIA)  ➽ more inventions...

Dolgor Bataar (NIA)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 8,795,674 issued 2014-08-05
U.S. Pat: 9,605,044 issued 2017-03-28
US Application No. 60/722,675
US Application No. 15/404,189
US Application No. 14/313,481

Publications:
D Baatar, P Olkhanud, D Newton, K Sumitomo, A Biragyn. CCR4-expressing T cell tumors can be specifically controlled via delivery of toxins to chemokine receptors. J Immunol. 2007 Aug 1;179(3):1996-2004. PubMed abs
M Coscia, A Biragyn. Cancer immunotherapy with chemoattractant peptides. Semin Cancer Biol. 2004 Jun; 14(3):209-218. PubMed abs
R Schiavo et al. Chemokine receptor targeting efficiently directs antigens to MHC class I pathways and elicits antigen-specific CD8+ T-cell responses. Blood 2006 Jun 15; 107(12):4597-4605. PubMed abs
D Baatar, P Olkhanud, K Sumitomo, D Taub, R Gress, A Biragyn. Human peripheral blood T regulatory cells (Tregs), functionally primed CCR4+ Tregs and unprimed CCR4- Tregs, regulate effector T cells using FasL. J Immunol. 2007 Apr 15;178(8):4891-4900. PubMed abs

Collaboration Opportunity:

The Immunotherapeutics Unit, National Institute on Aging, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Chemotoxin technology for clinical use or as a laboratory tool for depletion of cells. Please contact Nicole Darack, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information.


Licensing Contact:
Nicole Guyton,
Email: darackn@mail.nih.gov
Phone: 240-276-5530

OTT Reference No: E-027-2005-0
Updated: Sep 23, 2009