Chemotoxins: Specific Killers of Cancer Cells and Other Cells

Background:
The National Institute on Aging's Laboratory of Immunology demonstrated that chemokines can be used to deliver tumor antigens to dendritic cells and elicit anti-tumor responses. The Lab is seeking Cooperative Research and Development Agreement (CRADA) collaborator(s) to develop chemotoxins. A potential area of application is in anti-tumor therapy, specifically, immunotherapeutics for hematological malignancies such as leukemia/lymphomas and multiple myeloma.

Technology:
Recently, the Lab found that chemokines can also be used to deliver toxin moieties into cells expressing respective chemokine receptors to achieve specific deletion of these cells. Thus, these chemotoxins are an exciting new mechanism of tumor therapy. In addition, chemotoxins may also be used to preferentially deplete various immunosuppressive cells. Chemotoxins directly kill tumor cells that express chemokine receptors, such as CLL, multiple myeloma and cutaneous T-cell leukemia. In addition, chemotoxins may be injected systemically or locally into tumor sites to kill infiltrating immunosuppressive immune cells such as macrophages, NKT and T regulatory cells to upregulate the natural immune response.

Value Proposition:
Potential for personalized cancer therapy.

IP Status:
U.S. Patent Application filed in September, 2005

Development Status:

• LI has produced chemotoxins that target a number of chemokine receptors expressed by tumors. The TARC-chemotoxin has been shown to effectively eradicate established cutaneous T cell leukemia in mice. The CCL27-chemotoxin preferentially kills B16 melanoma cells that express chemokine receptor CCR10.
• Chemotoxins are also being used as a research tool to answer biology and immunology questions. For example, LI has demonstrated that the presence of immunosuppressive T regulatory cells can be efficiently depleted with TARC-chemotoxin to augment T cell responses.

Further R&D Required:

• Development of optimal purification and production strategies.
• Development of chemotoxins to all 18 chemokine receptors as a tool for studying various immunological questions.
• Full analysis of the potency of chemotoxins for treatment of human diseases and cancer.

Contact Information:
John D. Hewes, Ph.D., NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #374 ND

Updated 10/31/2007