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881 Enhanced antibody-mediated phagocytosis and antibody-mediated cell cytotoxicity using tetravalent, bispecific innate cell engagers (ICE®) in 3D spheroids
  1. Sheena Pinto,
  2. Savannah Jackson,
  3. Julia Knoch,
  4. Christian Breunig,
  5. Arndt Schottelius and
  6. Joachim Koch
  1. Affimed GmH, Heidelberg, Germany


Background The redirected optimized cell platform (ROCK®) enables the generation of customizable innate cell engagers (ICE®) of varying valency, affinity, and pharmacokinetic profiles. Preclinical and clinical studies have demonstrated the advantage and unique features of this first-in-class ICE® antibodies across a multitude of cancers and its differentiation to monoclonal antibodies. ICE® are tetravalent, bispecific antibodies that bivalently bind to a unique epitope on CD16A, which is selectively expressed on natural killer (NK) cells and macrophages, while the other domains target a tumor antigen. In addition to promoting antibody-dependent cellular cytotoxicity (ADCC) of NK cells, ICE® can also promote tumor targeting of macrophages eventually inducing antibody-dependent cellular phagocytosis (ADCP).

Methods ADCP and ADCC assays were performed using monocyte-differentiated macrophages and NK cells derived from healthy donor PBMCs. Target tumor lines and patient-derived xenograft line-derived spheroids were labelled and co-cultured with macrophages or NK cells. Live-cell imaging (IncuCyte®) was used to measure ADCP and ADCC events.

Results We show that ICE® molecules can enhance ADCP of tumor cells mediated by various functional/phenotypic subsets of macrophages derived from in vitro differentiation of human monocytes. ICE®-induced ADCP of tumor target cells was seen across different macrophage subtypes (M1 and M2). We further investigated the expression of immune-suppressive checkpoint programmed death-ligand 1 (PD-L1) on macrophages upon ICE® treatment that could be a key anti-tumor molecule within the suppressive tumor microenvironment. Based on patient-derived xenograft line-derived spheroids (3D) generated from primary tumor samples of patients suffering from various malignancies, we could demonstrate robust ADCC and ADCP mediated by NK cells and macrophages, respectively.

Conclusions ICE® molecules are able to mount robust NK cell- and macrophage-mediated anti-tumoral innate immune responses. This combined immune activity has the potential to not only fight tumor cells directly but also to initiate a full immune response comprised of innate and adaptive components of the immune system.

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