MKC 1106
MKC1106 is MannKind's Immunotherapy regimen under investigation for the treatment of various solid malignancies and melanoma.
Our immunology approach consists of a combination of innovative immunization vectors and a proprietary methodology to vaccinate against a broad range of tumor antigens.
Specifically, we use DNA- and peptide-based compounds that correspond to tumor-associated antigens that are expressed in a range of tumors. A patient's immune system is first "primed" by DNA plasmids that are injected directly into the patient's 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 (APC) that reside in the lymph nodes internalize our plasmids, express the encoded peptides and display the desired epitopes to central memory T-cells that are also present in the lymph node. In this manner, the T-cells of the immune system become sensitized to the tumor associated antigens encoded by our plasmids.
After several 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 strongly with MHC (major histocompatibility complex) molecules, the surface receptors that display epitopes to the immune system. The peptide injection greatly "boosts" the proliferation of central memory T-cells that target the desired epitopes and 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 (DNA) priming and peptide boosting, we believe that 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.
One of the distinctive features of our approach is our delivery method. In contrast to the conventional subcutaneous or intramuscular route of administration, our compounds are delivered directly into the patient's lymph nodes, sites rich in T-cells and APC. We believe that this delivery method ensures that T-cells are exposed to greater concentrations of antigens for a longer period of time than would occur after administration by other routes.
