PP-100: How it works
Pattern’s PP-100 product simultaneously activates four of the five Toll-like receptors (TLRs) found on the cell membranes of innate immune cells, predominantly TLR4, as well as TLR1, TLR2 and TLR6.
TLR4 was the first TLR identified in humans (1997) and is the most studied member of the TLR family.
TLR4 is unique among all other TLRs as it uses both MyD88-dependent and TRIF-dependent pathways, which allows TLR4 to induce a broader range of immune responses than other TLRs.
Pattern’s scientific co-founders discovered receptor clustering necessary to activate innate immune cells
PP-100 forms large clusters of receptors.
PP-100 activates DCs and macrophages, turning them into killer DCs and killer macrophages (while also activating NK cells & others) and driving the APC activities of these DCs and macrophages directed towards tumor antigens.
The activated cells include:
- Dendritic Cells (DCs) suppress cancers using IFN-β, TNF-α, TRAIL, Fas-L
- Macrophages (M1) kill tumor cells using the active radicals ROS, NO, peroxynitrite
- NK Cells kill tumor cells using perforin & granzymes
PP-100 thereby promotes adaptive immune reactions, thus resulting in anti-cancer cytotoxic T-cells, antibodies and long-term T-cell memory -enables elimination of distant metastatic cells.
PP-100 effect on DCs is to upregulate the key functions necessary for interactions with T cells as well as to generate new long-lived memory T cells & reactivate existing memory T cells.
PP-100 causes the production of:
- Key cytokines: TNFα, IL-1β, IL-6, IL-8 , IL-12, MCP-1, IL-17, RANTES, GM-CSF
- Membrane expression of costimulatory & MHC molecules: CD80, CD86, CD40, MHCI & MHCII molecules
- Effector mediators: nitric oxide, peroxynitrite
The result is a broad immune response which then returns to baseline as standard immune dampening mechanisms kick in.
Opportunities: Pipeline in a Product
Based on its mechanism of action, PP-100 may find application in a range of cancers, both as a monotherapy and in combination therapy.
Pattern’s initial focus is on HPV-related cancers. Despite the availability of preventive HPV vaccines, HPV prevalence remains high and HPV-associated cancers remain a significant health concern worldwide. It is estimated that 5% of all cancers worldwide (with more than 600,000 new cancer cases per year) are attributable to HPV.
Other pipeline opportunities for PP-100 include cancers caused by infections in general (15%+ of cancers), as well as other cancers more generally.
Based on data generated, PP-100 has other applications which Pattern may partner, including its use against infectious diseases, as a vaccine carrier or as an adjuvant.
Pattern has collaborated closely with the Massachusetts General Hospital (Harvard), the National Research Council of Canada (NRC), McGill University (Goodman Cancer Centre and TB Centre), and the University of Toronto.
Pattern is open to partnerships that will move its clinical programs forward and enhance the development of our internal pipeline.
Directors and Leadership
Mark de Groot, PhD
Director and CEO
Hans Keirstead, PhD
Nick Glover, PhD
John Abeles, MD
Ralph Landau, PhD
Head of CMC
Yann Rioux, MSc
Key Advisors and Employees
Mark Poznansky, MD, PhD
Clinical and Scientific Advisor
Frank Perabo, MD, PhD
Clinical and Scientific Advisor
CMC and Technical Advisor