Imprime PGG (Imprime), a soluble yeast 1,3/1,6 β-glucan, is being developed as a novel cancer immunotherapy in conjunction with anti-tumor antibodies in several cancers. Randomized Phase 2 clinical trials of Imprime in the 1st-line treatment of stage IV non-small cell lung cancer have shown promising efficacy in both objective tumor response and survival. Mechanistic work has revealed that Imprime acts to stimulate a coordinated, anti-cancer immune response in conjunction with antibody therapy. Imprime represents a pathogen associated molecular pattern (PAMP) that can be efficiently and effectively recognized by cells of the innate immune system. This can trigger macrophage repolarization, neutrophil activation, dendritic cell maturation, NK cell activation and, via cross-talk with the adaptive immune system, expansion of CD4 and CD8 T cells. Imprime’s 1,3/1,6 β-glucan polymeric structure allows for the straightforward attachment of proteins via several conjugation routes. Additionally, unlike other PAMPs that require intratumoral injection, Imprime is safely dosed systemically via iv injection. These properties make Imprime an excellent immune activating scaffold to which antibodies or other proteins can be attached. Three different approaches that utilize Imprime as a conjugation scaffold will be discussed. The first involves attaching Abs to make conjugates that mimic immune complexes formed naturally between fungal carbohydrate PAMPs and Abs of the immune system. The second approach involves the attachment of tumor specific mAbs or mAb fragments to deliver the PAMP to the tumor microenvironment. The third approach involves the attachment of proteins that can be delivered to dendritic cells to drive an adaptive immune response against the antigenic protein. The conjugation chemistry, analytical characterization, and biological activity of these conjugates will be discussed.

Activation of innate immune cells with antibody conjugates of a fungal derived pathogen associated molecular pattern molecule, Imprime PGG

251st National Meeting (2016)

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