Discover Combination Therapy

Follow the Data: Discovering preclinical differences in bispecific impact on T cell & tumor cell interactions¹

Research Area: Checkpoint & combination therapy

Development Stage: Discovery

Goal: Identify subtle differences and mechanism in therapies that engage T cells and the tumor microenvironment

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How our single-cell systems are making a difference

Solution: PSI revealed differences to enhance decision making

Finding: Enhanced bispecifics elicit more polyfunctional subsets than control when interacting with tumor target

Follow the data

PSI identified T cell potency upregulation triggered by novel bispecifics and revealed unique T cell cytokine mechanisms in response to tumor target. PSI was computed for CD4+ and CD8+ T cells; the profiles of both B2-OKT3 and hNKG2D-OKT3 showed significant polyfunctional upregulation relative to the Tz47-2C11 control sample, indicating their effectiveness in triggering a potent T cell response.

Both bispecific profiles are dominated by effector cytokines. hNKG2G-OKT3 stimulation is more potent in terms of polyfunctional strength index (PSI) than B2-OKT3, and sources of upregulation are revealed through the differential cytokine profile (i.e. chemoattractive and effector cytokines). CD4+ and CD8+ cells show the same trend and almost identical cytokine secretion with the exception of IL-5.¹

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IsoPlexis finds critical differences

PAT PCA visualization illustrates the differential T cell upregulation triggered by novel hNKG2D-OKT3 and B2-OKT3 bispecifics, by identifying highly functional cell subsets. CD4+ T cells from the hNKG2D-OKT3 group (orange) secreted polyfunctional effector proteins more frequently than those cultured in the presence tumor cells and the B2-OKT3 bispecific (blue).

This hNKG2D-OKT3 polyfunctionality includes diverse combinations of secretions, whereas B2-OKT3 overall elicited fewer polyfunctional and more monofunctional secretions. The increased polyfunctional response and T cell potency driven by hNKG2D-OKT3 indicates its potential superiority over B2-OKT3.¹

[1] Reference: Zhou et al, SITC Annual Meeting 2018