We propose a series of experiments which evaluate methods to increase potency of a plasmid DNA tumor vaccine being developed for the treatment of low grade non-follicular lymphoma. Based on the results of pre-clinical tumor challenge studies in a mouse lymphoma model system and a Phase I/II clinical trial in B-cell lymphoma patients, we have demonstrated that a novel bicistronic plasmid DNA vector, designed to elicit an anti-idiotype immune response when injected into muscle tissue, can protect animals from idiotype tumor cell challenge and can generate immunogenicity in humans. More recent pre-clinical studies indicate that co-injection of a second DNA plasmid, expressing the murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), increases immunogenicity and long-term protection in animals relative to the idiotype expression plasmid alone. The series of pre-clinical experiments presented here are designed to further increase the potency of this multivalant plasmid vaccine in mice and, in turn, rhesus monkeys. We anticipate that these experiments will lead to a more potent tumor vaccine which will be tested in B-cell lymphoma patients in a second clinical trial. We also anticipate that success of this therapeutic vaccine will lead to the use of DNA vaccines to treat a wide range of human cancers.

Proposed Commercial Applications

There is presently no curative therapy for the treatment of low-grade follicular lymphoma in humans. This work will advance the development of a novel tumor vaccine which is showing promise in B-cell lymphoma patients. This DNA vaccine is designed to develop an anti-idiotype immune response and thereby suppress or eliminate tumor metastases. Developments in DNA technologies, such as robotic cloning and characterization of genes, will make commercial development of patient- specific vaccines feasible.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA082952-01
Application #
2903480
Study Section
Special Emphasis Panel (ZCA1-SRRB-Y (M2))
Program Officer
Muszynski, Karen
Project Start
1999-07-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Vical, Inc.
Department
Type
DUNS #
183192855
City
San Diego
State
CA
Country
United States
Zip Code
92121