Active Immunotherapy Platform
Our immunotherapy approach is built on the observation that direct intra-lymph node administration of immune active compounds affords regulation of immune responses, due to co-localization within lymphoid organs of various types of cells important to this function.
Data demonstrate this delivery method ensures T cells are exposed to greater concentrations of antigens for a longer period of time than would occur after administration by other routes. A crucial goal of cancer therapy is to afford long-term control of the cancer process with reduced side effects and effective enhancement and modulation of durable, anti-tumor immunity. Intra-lymph node immunization enhances this potential and is feasible as demonstrated by our preclinical data and confirmed in our Phase 1 proof-of-principle study.
We use DNA and peptide reagents to stimulate an immune response that targets tumor-associated antigens which are expressed in a range of tumors. A patient’s immune system is first “primed” by DNA plasmids that are injected directly into accessible, non-diseased, superficial inguinal lymph nodes. These plasmids encode fragments of tumor-associated antigens, encompassing specific epitopes that are presented on the surface of tumor cells. Antigen Presenting Cells that reside in the lymph nodes take up our plasmids, express the encoded peptides, and display the desired epitopes to specific T cells that are also present in the lymph node. In this manner, the T cells of the immune system effectively become sensitized to the tumor-associated antigens encoded by our plasmids.
After repeat priming injections, the patient’s lymph nodes are then injected with synthetic analogs of the desired epitopes. These peptides, containing sequence substitutions that greatly enhance their pharmacological properties, are designed to bind with Major Histocompatibility Complex molecules, the surface receptors that display epitopes to the immune system. The peptide injection effectively “boosts” the proliferation of specific T cells that target the desired epitopes. This further stimulates their differentiation to “killer” or cytotoxic T cells, with a greater ability to migrate to tumor site and metastatic lesions throughout the body, where they destroy tumor cells. By repeating the cycle of plasmid priming and peptide boosting, we can initiate, deploy and regenerate a potent cell-mediated immune response that targets cancer cells along with (in the case of certain vaccine constructs) the underlying blood supply.
Key Program Highlights
- Intra-lymph node delivery
- Approach is applicable across tumor types
- Synthetic, off-the-shelf injectable products
- Targeted, biomarker-guided therapy