We utilize proprietary mRNADis and mSCAFold platforms to precisely engineer biologics and modulate immune activation. We will report the discovery and preclinical studies of EPIM-001, a bispecific IL2/PD-L1 biologics that has demonstrated multiple mechanisms of action and potent anti-tumor activity; EPB-001, a human anti-Siglec15 antibody that reversed immune suppression and inhibited tumor growth.  EPIM-001 and EPB-001 could be promising therapeutics for tumors that are non-responding or resistant to immune checkpoint inhibitor treatment.

Abcam is committed to quality and supporting efforts to address the reagent reproducibility crisis. In this talk, Deborah Moore-Lai will discuss biophysical characterization of protein reagents for batch-to-batch reproducibility, providing an overview of Abcam's Premium Bioactive Proteins and analytical tools for assessing physical and functional characteristics of the product line.

Blockade of the inhibitory checkpoint programmed-death 1 (PD-1) can be an effective immunotherapy for cancers, but many patients do not respond, and the mechanisms that drive resistance are not well understood. We investigate how the intrinsic properties of tumor-specific T cells and the overarching influence of T cell receptor affinity determine T cell responsiveness to PD-1 blockade. Our work has the potential to identify new strategies for overcoming therapeutic resistance to PD-1 blockade.

CD22 CAR T cell therapies have shown efficacy in relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) alone and in combination with CD19 CAR T cell therapies. We identified novel single domain antibodies (VHH) to CD22 for CAR-iNK immunotherapy in B-ALL and formatted as CARs, both in monovalent and tandem, bivalent formats.  The combination of two VHHs in tandem, binding to both N- and C-terminal epitopes is most effective at eliminating CD22-positive tumor cells.

Evaluation of Fc effector mechanisms of the therapeutic antibodies is an important regulatory requirement. Eurofins DiscoverX’s MOA-reflective KILR cytotoxicity assays specifically measure direct killing of antigen-expressing target cells in co-culture with effector cells mediated via ADCC using an easy-to-use, dye-free, and radioactivity-free protocol. Here we share phase-appropriate qualification data for the KILR Raji bioassay model demonstrating that these assays are fit-for-purpose for screening and relative potency applications in lot-release testing.

Gamma delta T cells are a unique class of lymphocytes that bridge innate and adaptive immunity.  Adaptate has developed monoclonal and bispecific antibodies which target gamma delta T cells. These antibodies selectively modulate gamma delta T cell activity with a potential for superior efficacy and safety compared to conventional immunomodulatory therapies such as pan T cell activators and are being developed primarily for solid tumour indications.

The Retrogenix Cell Microarray technology identifies on- and off-target binding for a range of therapeutic modalities by profiling against >6,300 human cell surface and secreted proteins - now including human prenatal targets - each expressed in human cells. Data generated can inform lead selection decisions and provide IND-enabling data for regulatory submissions, accepted by global regulators either in complement with, or as an alternative for, IHC-based tissue cross reactivity data.

The job of an immunotherapy drug is to instruct the adaptive immune system – in other words, to act as a vaccine. This process is well understood to be a highly local one, leading to a groundswell of intratumoral immunotherapy efforts. We will present our recent work developing new molecules and recently published design principles for such intratumoral immune therapeutics, as well as unpublished data from our ongoing clinical trial treating companion dogs with naturally occurring melanoma and soft tissue sarcoma.

Ankyra’s platform enables stable tethering of cytokines and other immune agonists to the common vaccine adjuvant aluminum hydroxide through a novel phosphopeptide linkage. When administered intratumorally (IT), these complexes form an extended depot in the tumor leading to prolonged immune activation and potent local and systemic anti-tumor efficacy after a single injection with minimal toxicity.

Berkeley Lights’ Optofluidic platforms enable deterministic isolation and culturing of single or multiple cells in nanoliter-sized chambers, allowing for sequential functional assays on the same cell sample, thereby linking cytotoxicity and cytokine secretion. We recently demonstrated organoid structure formation on chip and are looking to use this capability in tumor microenvironment research.

Despite CAR T cell therapy success in hematological malignancies, toxicities following CAR T cell therapy remain a main limitation to the wider application of the therapy for the treatment of diseases. Here we will discuss lessons learned with regard to mechanisms of toxicities after CAR T cell therapy and review new directions to mitigate such toxicities.

The most common severe toxicity associated with chimeric antigen receptor T cells targeting CD19 (CART19) is cytokine release syndrome (CRS). To obtain a more robust understanding of CRS biology, we performed comprehensive secretome profiling to measure more than 1400 serum analytes on serial serum samples collected from patients treated with the 41BB-containing CTL019 on two clinical trials. We identify pre-infusion biomarkers for CRS and potentially targetable pathways.