Targeting B-cell lymphoma with Leukothera-phase II

Information

  • Research Project
  • 8831094
  • ApplicationId
    8831094
  • Core Project Number
    R42CA173900
  • Full Project Number
    2R42CA173900-02
  • Serial Number
    173900
  • FOA Number
    PA-14-072
  • Sub Project Id
  • Project Start Date
    9/27/2012 - 12 years ago
  • Project End Date
    8/31/2016 - 8 years ago
  • Program Officer Name
    HAIM, TODD E.
  • Budget Start Date
    9/26/2014 - 10 years ago
  • Budget End Date
    8/31/2015 - 9 years ago
  • Fiscal Year
    2014
  • Support Year
    02
  • Suffix
  • Award Notice Date
    9/26/2014 - 10 years ago
Organizations

Targeting B-cell lymphoma with Leukothera-phase II

DESCRIPTION (provided by applicant): B-cell lymphoma is cancer of B-lymphocytes and accounts for more than 20,000 deaths in the U.S. each year. While many patients respond to currently available therapy, there is a high rate of cancer relapse and inability for the patients o tolerate chemotherapy. Thus, there is a significant need to make available to these patients newer therapies that are more effective and better tolerated than the drugs that are currently used. Actinobac Biomed, Inc. is developing a natural biologic therapy that seeks out and kills a subset of white blood cells (WBCs). This therapy, Leukothera(R) (LtxA; leukotoxin), is a native protein derived from an oral bacterium. LtxA binds specifically to the active form of lymphocyte function associated antigen- 1 (LFA-1) and causes cell death. LFA-1 is found exclusively on WBCs, and malignant WBCs overexpress the molecule, making them ideal targets for the drug. During the phase I stage of this STTR application, we showed that 1) LtxA kills malignant B-cells using a unique mechanism of action, which involves Fas death receptor and caspase 8; 2) lymph node tissue samples from B-cell lymphoma patients express high levels of LFA-1; 3) LtxA causes complete regression of tumors in a humanized mouse model for B-cell lymphoma and results in long-term survival; 4) the drug is well-tolerated, highly active, and does not cause a neutralizing immune response in healthy dogs or a dog with naturally-occurring lymphoma, and 5) we have initiated expression and production of recombinant LtxA in a cGMP drug manufacturing facility in preparation for Investigational New Drug (IND)-enabling studies and clinical trials. Important pharmaceutical properties of LtxA include: 1) the drug works rapidly in vivo, within minutes or less; 2) doses as low as 0.5 g/kg have been shown to be highly active in animals; 3) neutralizing antibody to LtxA is not generated in healthy or diseased animals, even after repeat dosing; and 4) the high specificity of the drug allows targeting of a subset of WBCs and complete depletion of WBCs has never been observed with LtxA treatment. During this STTR phase II proposal, Actinobac will carry out IND-enabling studies that will be included in the IND application to the FDA.

IC Name
NATIONAL CANCER INSTITUTE
  • Activity
    R42
  • Administering IC
    CA
  • Application Type
    2
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    905040
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    350
  • Ed Inst. Type
  • Funding ICs
    NCATS:38487\NCI:866553\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    ACTINOBAC BIOMED, INC.
  • Organization Department
  • Organization DUNS
    829616676
  • Organization City
    NORTH BRUNSWICK
  • Organization State
    NJ
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    089023378
  • Organization District
    UNITED STATES