We are advancing a robust pipeline of therapeutic agents designed to modulate the Cancer Immunity Cycle through multiple mechanisms and targets, including cancer cells, components of tumor microenvironments (TMEs) and various types of immune cells.
Each dot on an arrow represents a distinct A-Kine program. Each A-Kine is unique in its mechanism of action
The A-Kine programs contained in the pipeline integrate multiple re-engineered cytokine types, including interferons (IFNs), interleukins (ILs) and tumor necrosis factors (TNFs), with multiple unique targeting modules that guide conditional cytokine action to target cells of interest. The plug-and-play assembly of A-Kine modules, which includes proprietary molecular scaffold and linker frameworks, facilitates the design and generation of a diversity of agents, each with unique properties.
Through targeted modulation of the adaptive and/or innate immune system and TMEs, A-Kines are optimized to deliver effective single agent activity across a range of tumor types, including immunologically “cold” solid tumors and tumors refractory to standard immune checkpoint inhibitor strategies. Additionally, A-Kines have the potential to synergize with other treatment paradigms, including small molecule therapies, radiotherapy, checkpoint inhibitors and cell therapies.
The objective of our pipeline strategy is to advance multiple complementary and synergistic approaches to overcome the intrinsically immunosuppressive tumor microenvironment, and to unleash an effective immune response against a broad spectrum of human cancers. This includes cancers that exhibit an intrinsically low or absent immune involvement and thus are particularly challenging therapeutic targets. Our approaches involve the removal of various cancer-imposed brakes on components of the immune system, as well as targeted activation of and enhancement of infiltration of tumors by cancer-inhibitory immune cells, such as cytotoxic T cells (CTLs). Induction of lasting memory T cell responses to promote cancer immunity is our ultimate goal.
CIC Phase 1 - Detection
Antigen Presenting Cells (APCs) detect tumor antigens in necrotic tumor mass. Antigen uptake is associated with APC activation (priming)
CIC Phase 2 - Activation
Primed APCs activate and promote proliferation of tumor antigen-specific T cells (lymph node). Chemokines released from activated APCs act as chemotactic signals for recruitment of various immune cells (tumor).
CIC Phase 3 - Infiltration
Activated T cells (CTLs) reach and infiltrate tumor through tumor neovasculature. Multiple mechanisms regulate infiltration.
CIC Phase 4 - Killing
Infiltrated CTLs recognize and kill tumor cells. Activity of CTLs and viability of tumor cells is influenced by other cells and components of the tumor microenvironment (TME).
Desired outcome - Cancer immunity
Activated T cells may become memory T cells, which have the potential to impart long term cancer immunity.