Nogapendekin alfa

Interleukin-15 (IL-15) regulates natural killer (NK) and memory T cell homeostasis, making it a notable therapeutic target for cancers and immune disorders such as HIV. For example, it is a mediator of NK cell and T cell activation and proliferation. IL-15 signals through a heterotrimeric receptor that is composed of the common gamma chain (γc) subunit, the beta chain (βc) subunit, and the IL-15-specific alpha subunit (IL-15Rα). IL-15 and IL-15Rα are typically presented by antigen-presenting cells, like monocytes and dendritic cells. These cells present IL-15 in a complex with IL-15Rα to neighbouring immune cells — specifically, natural killer (NK) cells and CD8+ T cells which have the CD122/CD132 receptor complex (shared IL-2/IL-15 receptor; βc and γc). In other words, IL-15 is trans-presented by the IL-15Rα.

Nogapendekin alfa is administered as a stable heterodimeric complex with inbakicept, which mimics the biological actions of IL-15. Nogapendekin alfa is a human IL-15N72D variant that has an asparagine (Asn) to aspartate (Asp) mutation at amino acid 72 (N72D), which grants the drug increased biological activity and a longer serum half-life compared to free IL-15. The binding of the nogapendekin alfa-inbakicept protein complex to IL-15 receptor promotes the proliferation and activation of NK, CD8+, and memory T cells without the proliferation of immuno-suppressive Treg cells. In a carcinogen-induced model of bladder cancer in immunocompetent rats, intravesicular administration of nogapendekin alfa-inbakicept alone or in combination with BCG showed anti-tumour activity.