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 Applications

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA089856-01
Application #
6292666
Study Section
Special Emphasis Panel (ZRG1-SSS-1 (01))
Program Officer
Muszynski, Karen
Project Start
2001-08-01
Project End
2002-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$287,382
Indirect Cost
Name
Antigen Express, Inc.
Department
Type
DUNS #
956062384
City
Worcester
State
MA
Country
United States
Zip Code
01606
Lu, Xueqing; Kallinteris, Nikoletta L; Li, Jizhi et al. (2003) Tumor immunotherapy by converting tumor cells to MHC class II-positive, Ii protein-negative phenotype. Cancer Immunol Immunother 52:592-8