NOVEL PD1-TARGETED IL-15 IMMUNOCYTOKINE and VITOKINE FUSIONS

Abstract

The present disclosure provides novel PD1 Ab-IL-15 immunocytokine and VitoKine compositions that aim to target potency-attenuated or bio-activable IL-15 directly to tumor-infiltrating lymphocytes to reduce systemic mechanism-based toxicities and lead to broader therapeutic utility for IL-15 for the treatment of cancer. Potency attenuation of IL-15 in PD1 Ab-IL-15 immunocytokine improves target selectivity, facilitates the establishment of stoichiometric balance between the cytokine and antibody arms, and helps alleviate pathway over-activation and mitigate antigen sink and target-mediated deposition. IL-15 in PD1 Ab-IL-15 VitoKine will remain until activated locally by proteases that are upregulated in diseased tissues, this will prevent over-activation of the pathway and reduce undesirable “on-target” “off tissue” toxicities, and significantly decrease the potential antigen or target sink, and thus, prolong the in vivo half-life and result in improved biodistribution, bioavailability and therapeutic efficacy. In both PD1 Ab-IL-15 immunocytokine and VitoKine, PD1 antibodies capable of blocking PD1 and reversing T-cell anergy or exhaustion may further synergize with IL-15 anticancer immune response.

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