ILT3 Binding Molecules for Immune Modulation

The patent applies inversion by designing binding molecules that produce opposite effects in different contexts: in vitro, the molecules downmodulate immune cell activation and reduce inflammatory cytokine production; however, in vivo, the same molecules upmodulate immune responses and enhance immune stimulation. This context-dependent inversion allows the molecules to serve dual purposes as both immune controllers and stimulators.

The patent utilizes parameter changes by modifying the binding molecules through various embodiments including different affinities (e.g., KD values), isotypes (IgG1, IgG2, IgG3, IgG4), and structural variations (full-length antibodies, fragments, humanized versions). These parameter changes enable the molecules to achieve different functional outcomes in different biological contexts, resolving the contradiction between in vitro suppression and in vivo stimulation.

The patent applies local quality by designing binding molecules with high affinity for a specific local target (ILT3 on antigen-presenting cells) while maintaining overall safety. The molecules exhibit selective binding to ILT3 with KD values ranging from 10^-9 to 10^-12 M, achieving precise local action at the intended target site while minimizing off-target effects through this localized specificity.

The binding molecules serve as intermediaries that selectively engage ILT3 to modulate immune responses. By using these intermediate binding molecules with controlled affinity and specificity, the patent achieves precise immune regulation without direct harmful effects, as the molecules themselves are not pathogenic but rather mediate the immune modulation through their specific binding to ILT3.