Abstract 1729: Integrative immune profiling of syngeneic tumor models provides predictive immune signatures for treatment response with HMBD002, a novel anti-VISTA neutralizing antibody

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.1729-1729
• Main Authors: Boyd-Kirkup, Jerome D., Thakkar, Dipti, Paszkiewicz, Konrad, Ingram, Piers J.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2018-1729

Myeloid-derived suppressor cells (MDSCs) are a group of immature myeloid cells with potent immune suppressive activity. Accumulation of pathologically activated MDSCs within the tumor microenvironment has emerged as an important mechanism of primary and acquired resistance to immunotherapy. MDSCs have high surface expression levels of V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation (VISTA), a co-inhibitory negative checkpoint regulator (NCR). Immune suppression by VISTA+ MDSCs has been implicated in the failure of, and resistance to, anti-PD1/PDL1 therapy and represents a unique axis for NCR targeting in the non-responder population. Elucidating the dynamics of VISTA+ MDSCs within tumors is imperative for predicting response and patient stratification. HMBD-002 is a novel anti-VISTA neutralizing monoclonal antibody, developed using Hummingbird Bioscience's proprietary Rational Antibody Discovery platform, against a specific functional epitope on VISTA predicted to be involved in ligand binding. HMBD002 binds human, cyno and murine VISTA protein with high affinity (kD