COMBINED IL-2 AND MHC CLASS II GENE THERAPY FOR CANCER
DESCRIPTION: Antigen Express has developed technology to force the presentation
of endogenous tumor antigens in a manner that produces an effective tumor cell
vaccine. The key to this strategy is the generation of tumor cells that express
MHC Class II molecules in the absence of the MHC Class II associated invariant
chain (Ii protein). We are now developing an in vivo gene therapy strategy for
inhibition of Ii protein expression (using Ii reverse gene constructs) in
tumors. As not all tumors are MHC Class II positive, we are combining Ii
inhibition with IL-2 and/or MHC Class II transactivator (CIITA) gene therapy.
IL-2 is advantageous in that it stimulates the expansion of antigen specific T
cells and causes interferon-gamma production (which is a good inducer of MHC
Class II molecules) while CIITA is a potent and direct MHC Class II inducer. We
will establish the ability of IL-2 and CIITA gene therapy vectors to induce MHC
Class II molecules in vivo using a murine renal cell carcinoma model and an
ovarian ascites model. Selective inhibition of Ii will be accomplished using a
reverse gene construct. Finally, we will establish the therapeutic efficacy of
combined IL-2 (or CIITA) and Ii reverse construct gene therapy on established
Renca tumors and MOT ascites in vivo. Success will trigger Phase II studies,
wherein we will develop appropriate constructs using human gene sequences,
demonstrate activity in primary human tumor samples and complete all necessary
studies requisite to an IND filing.
PROPOSED COMMERCIAL APPLICATION:
Immunotherapy represents a novel form of cancer therapy that complements existing
treatment modalities. Successful demonstration of the augmentation of tumor immunogenicity
in a manner that generates a robust anti-tumor immune response will satisify a significant
unmet need in modern health care.
Small Business Information at Submission:
Principal Investigator:Minzhen Xu
ANTIGEN EXPRESS, INC.
1 INNOVATION DR WORCESTER, MA 01605
Number of Employees: