Main Conference Day 3 - BST (British Summer Time, GMT+1)
We have shown that immune sex differences are involved in shaping the TME of pancreatic cancer and can be targeted for gender-specific immunotherapy. These differences highlighted the G-protein coupled receptor FPR2 and found that antagonizing FPR2 in myeloid cells has a remarkable effect on restoring T cell anti-tumor activities and reversing immunosuppressive myeloid cell function exclusively in females.
ImmTACs are TCR-based bispecific molecules designed to activate potent T-cell response to kill tumour cells. Here we present engineering of IMC-R117C ImmTAC targeting peptide derived from PIWIL1, a novel colorectal cancer target, in the complex with HLA-A2. Optimized TCR discovery and affinity engineering approach ensured high TCR specificity, as demonstrated by IMC-R117C ability to mediate potent and specific T-cell activation and killing of PIWIL1+ cancer cells, while sparing PIWIL1- cells.
Our immune system interacts with diseases in a multidimensional manner involving substantial biological, chemical, and physical exchanges. My lab aims to develop novel strategies to engineer the multidimensional immunity-disease interactions to create safe and effective therapies against cancer. In this talk, I will present a chemical approach, termed “switchable” immune modulator, to limit the systemic exposure and therefore ameliorate the toxicities of immune stimulatory antibodies and cytokines.
The presentation will describe the development of BI-1910, which is a strong FcgR independent TNFR2 targeting agonist. It will highlight cell types agonized, the induced change in cell composition and cytokine milieu in the tumor, and the therapeutic outcome in preclinical studies. I will also describe the toxicology result and the entering into a Phase I clinical trial.
Bivalent binding of antibodies is critical for their function but we lack an understanding of the factors determining bivalent binding. Here, we introduce a new method to analyse bivalent binding of antibodies in surface plasmon resonance. We find that the molecular reach, which is the maximum antigen separation distance that still allows a single antibody to reach them both, produces the best correlate of antibody function.
This presentation will discuss: 1) Genmab’s HexElect® technology is based on Fc-domain engineered IgG antibody pairs that act as Bio-Logic AND gates selectively activated after hetero-oligomerization; 2) Single molecule studies demonstrate how antibodies can dynamically assembly into higher-order structures after cell surface binding and 3) How we explore the potential combinatorial target space of HexElect using a combination of assays and predictive modeling.
Here we report a first-in-class disulfide rebridging and click-chemistry-based method for the generation of Fc-containing, IgG-like mono- and bispecific antibodies. These are in the FcZ-(FabX)-FabY format, i.e., two distinct Fabs and an Fc, potentially all from different antibodies, attached in a homogeneous and covalent manner. We have dubbed these molecules synthetic antibodies (SynAbs). We have also adapted this platform to make a trispecific, first-in-class, checkpoint inhibitory T cell engager (CiTE).