PolyStart Enhancing the visibility of cancer or infected cells to a patient’s immune system is a critical aspect of an effective vaccine. In this regard, TapImmune’s PolyStart nucleic acid-based technology provides a four-fold increase in target-cell-specific naturally processed antigenic epitopes on a cells surface. This increased cell surface presentation increases activated helper and/or long-lived killer T-cell populations that then effectively seek out and destroy a patient’s cancer cells.
To do this, the PolyStart portion of TapImmune’s novel nucleic acid-based technology is directly linked to a Poly-Antigen Array (PAA) portion encoding one or more of the above mentioned antigenic epitopes derived from one or more protein marker(s) overexpressed by a cancer cell. The four-fold increase in expression is mediated by a series of non-conventional mRNA translation start codons. The four-fold increase in PAA translation product is then naturally processed through the proteasome into small peptide antigenic epitopes which traffic to the cell surface in complex with an appropriate HLA Class I or II where a patient’s T-cells can bind to it. This increased cell surface expression subsequently increases the capacity for helper and/or killer T-cell recognition, activation and expansion.
For example, consider the case of a PAA encoding a multiple of four distinct antigenic epitopes; you can visualize this four-fold increase in expression as a collective and simultaneous increase in blue, red, green and yellow arrows, all of which are targeting a different antigenic epitope expressed by the same cancer cell. Thereby, TapImmune’s PolyStart technology is capable of not only providing an increase in the number of antigenic epitopes displayed but is also capable of providing this increase in context with four distinct opportunities to kill a single cancer cell.
The below data from a current study showing the increased presentation and subsequent KILLING of the targeted cell population.
TAP Vector Expression Platform Antigen System TAP (Transporters associated with Antigen Processing) is a central component of the immune system responsible for the processing of antigens and their subsequent presentation to the body’s immune system. TAP-based products have unique and broad application as vaccines for the treatment of both cancer and infectious disease.
In many solid cancer tumors the TAP protein system is down-regulated (greatly reduced or switched off) so that the immune system does not recognize and is not stimulated to attack the cancer. Restoration of TAP function in tumor-bearing animals results in significant reduction in tumor mass and prolongation of survival. TapImmune believes that this approach could become a central treatment for a wide variety of cancers in addition to making other cancer vaccine approaches more effective. In addition, our approach is potentially synergistic to existing therapies.
In the treatment of infectious disease, the use of the company’s TAP technology can make vaccines for microbial pathogens significantly more effective. In animal models vaccines (e.g.smallpox) were 100-1000 times more effective or potent in the presence of TAP vaccines. This offers a highly sought after solution to situations where in a pandemic outbreak like bird flu or H1N1 or a bioterrorism threat, vaccines are insufficient to meet demand. It also means that the amount of vaccine required per dose would be significantly reduced.
Infectious Disease and National Preparedness is another very significant market and ideal therapeutic area for the TPIV vaccine conjugate. Along with novel peptides and the PolyStart expression system the TPIV vaccine platform can address multiple infectious diseases as well as pandemic and biodefense threats. Our current Smallpox vaccine study at Mayo Clinic has already shown significant benefits over the current vaccine stockpile. It is naturally processed and peptide based, making it safer, longer lasting, cheaper and as effective (in animal studies) as the current product stockpile. The last DHHS contract for a smallpox vaccine stockpile was worth up to $2.8 billion.
This is a new paradigm and the next logical step in the treatment of cancer and infectious diseases, and could significantly advance the development of new vaccines as well as improve those that already exist.