The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. As part of the immune defense against disease, these immune cells are primarily involved in recognizing and targeting the destruction of foreign invaders and abnormal cells, such as virally infected cells and tumor cells. Thus, the National Cancer Institute (NCI) has previously listed IL-15 as the most promising product candidate that could potentially cure cancer. Our proprietary IL-15 platform utilizes the potency of IL-15 to provide ideal immunotherapeutic product candidates with broad applications for cancers and viral infections that can also be used as powerful adjuvants in combination therapies.
We are developing unique IL-15 superagonists based on our proprietary IL-15 technology. The lead molecule in this category is ALT-803, a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. ALT-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.
Preclinical studies have shown that ALT-803 simultaneously mobilizes both the innate and adaptive arms of the immune system to elicit rapid and durable responses against numerous cancers and virally-infected cells. Due to its robust immunostimulatory capacity for NK and T cells, we are developing ALT-803 for oncology and infectious disease indications. Furthermore, we are also exploring new applications for ALT-803 based combination approaches with other immunotherapies to further boost the immune response.
Altor is building on our IL-15 technology to create a next-generation targeted IL-15 scaffold platform to recognize and target specific antigens found in various cancers and viral infections. We have adapted the IL-15 superagonist complex to create a functional scaffold for the design of multi-specific fusion protein complexes. Using an antibody or single-chain T cell receptors (STARTM) as recognition domains linked to the IL-15 scaffold, we have generated both bivalent and bispecific product candidates (TxM).
Extensive characterization of these product candidates consisting of therapeutic antibodies and this scaffold indicates that such a targeted immunotherapeutic can potentiate the anti-tumor activities of the therapeutic antibody as well as potently facilitate immune responses. Thus, we are utilizing this IL-15 scaffold platform to generate multiple targeted IL-15 product candidates that can simultaneously promote killing of target cells and retain immunostimulatory functions of IL-15.