Immnocytokines have the potential to impact the broader pleotropic tumor microenvironment, more so than immune checkpoint inhibitors. That impact could perhaps be enhanced by radiation therapy. Multiple studies are currently in development at the NCI to explore this combination in prostate cancer.

Development of novel modalities to target WT1 provides a significant opportunity to address high unmet need in WT1-positive malignancies. CUE-102 Immuno-STAT biologics contain either HLA-A*02 or HLA-A*24 molecules, four copies of affinity-attenuated human IL-2, and an effector attenuated IgG1 Fc domain. CUE-102 selectively expand a polyfunctional, oligoclonal population of WT1 specific CD8+ T cells capable of recognizing and responding to WT1 peptide-presenting target cells. CUE-102 ImmunoSTATs have the potential to enhance anti-tumor immunity in patients with WT1-positive malignancies.

NKTR-255 is an interleukin-15 (IL-15) receptor agonist, which is currently being evaluated in a Phase 1 clinical study in patients with multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL). NKTR-255 is designed to work by selectively targeting the IL-15 pathway to expand both natural killer (NK) cells and memory CD8 T cell populations. This presentation will cover the role of NKTR-255 in enhancing NK functions to synergize in multiple myeloma setting. Role for NKTR255 in providing stemness to CD-19 CAR T cells will also be covered.

Next-generation protein biologics show great promise in the immunotherapeutic space. Many of these promising therapies struggle to find a cell line fit for commercialization. AbSci’s groundbreaking cell line development technology enables rapid development of scaleable microbial cell lines for the production of complex proteins at high titer and good quality.

This talk will cover the journey from discovery, through the Phase 1 experience, to pivotal studies of a novel bifunctional fusion protein designed to simultaneously inhibit the PD-L1 and TGF beta pathways.

XPATs are conditionally active T cell engagers that are activated by elevated protease activity in the tumor microenvironment. Unstructured polypeptides called XTEN provide long in vivo half-life and universal masking, while protease release linkers enable unmasking in the tumor microenvironment. In vitro activity of XPATs is attenuated >10,000-fold relative to unmasked forms. Masking provides >100-fold safety benefit in primate studies.