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FEATURED SESSION

EMERGING AGONIST AND ANTAGONIST TARGETS

Unlocking the Full Potential of Agonist Antibodies: A Multi-Faceted Challenge

Robert B. Stein, M.D., Ph.D., CSO, Agenus

Recent work on activating checkpoint targets such as GITR and OX40 has revealed that in addition to their co-stimulatory potential to enhance T cell responsiveness to tumor associated antigens, they are also highly expressed by activated intratumoral regulatory T cells. A more complete picture of the anti-tumor potential of GITR or OX40 agonist antibodies emerges when their regulatory T cell depleting capacity is considered. A review of selected findings supporting this picture will be presented.

Preclinical Evaluation of JTX-2011, an Anti-ICOS Agonist Antibody

Deborah Law, D. Phil. CSO Jounce Therapeutics, Inc.

ICOS (inducible co-stimulator molecule), a member of the CD28 superfamily, is a co-stimulatory molecule expressed on T lymphocytes. We have generated agonistic anti-ICOS antibodies which are efficacious as monotherapies and in combination with anti-PD1 in multiple syngeneic tumor models. Mechanistic studies demonstrate enhanced cytotoxic CD8:T-regulatory cell ratios and preferential reduction in T-regulatory cells in the tumor microenvironment. JTX-2011, a species cross-reactive humanized antibody, has been selected for development. Evaluation of JTX-2011 in nonhuman primate models, including safety and PK parameters, will be presented. Our preclinical data provides rational for clinical development of JTX-2011 in solid tumor indications.

Immunoregulation by VISTA in the Tumor Microenvironment

J. Louise Lines, Research Scientist, Microbiology & Immunology, Dartmouth College

VISTA is a recently identified PDL1/PD1-like ligand/receptor that is being developed as a target for cancer immunotherapy. VISTA blockade is therapeutic in CT26 cancer and synergizes with PD1 blockade. VISTA is highly expressed on tumor infiltrating myeloid cells, and impacts on myeloid function. Tumors from anti-VISTA treated mice show increased myeloid cells overall, but decreased granulocytic-MDSCs. This unique feature of anti-VISTA treatment may explain why it works well in combination with anti-PD1.