Preclinical and clinical evidence supports the ability of focal tumor radiotherapy (RT) in combination with CTLA4 blockade therapy to induce the activation and expansion of tumor-specific T-cells. I will present recent data showing that RT drives increased clonality of intratumoral CD8 T-cells, while CTLA4 blockade drives polyfunctional cytokine-producing CD4 and CD8 T-cells, and in combination they lead to the development of an effective anti-tumor immune response.

Multiple obstacles need to be overcome to prevent resistance to CAR T cell therapy of solid tumors. These include abnormal of adhesion molecule expression on the tumor vasculature, leading to reduced transmigration of effector immune cells including CAR T cells, and immunosuppressive cues in the tumor microenvironment, including regional hypoxia. The potential synergy between cytotoxic therapies and immunotherapies offers a strategy to safely overcome therapy resistance in solid tumors. I will provide an overview of the current developments in CAR T cell therapy and highlight the unique opportunities and challenges in combining CAR T cell therapy with radiotherapy.

High-through, small-scale protein purification has become a necessary tool in many areas of the antibody drug discovery and development process. Pipette tip-based chromatography columns, PhyTip columns, have proven to provide key solutions to many challenges in automating this process. Biotage PhyTip columns have already accelerated many user workflows in a wide array of applications. And new applications for pipette tip purification are completing these automation workflows.

The force of natural evolution determines the intrinsic complexity of our immune system that can’t be surpassed by in vitro design. Biocytogen established immunoglobulin humanized mouse platforms: RenMab, RenLite and RenMab HiTS. These platforms have been proved to generate high-quality antibody hits that show solid developability. RenLite is a powerful tool for bispecific antibody discovery, RenMab HiTS breaks immune tolerance and shows hyper immunity against challenging targets.

Embarking on a new drug discovery project is fraught with risk. The correct choice of target and therapeutic hypothesis is key to success. I will describe how the Open Targets program integrates data generation and bioinformatics to provide an integrated target identification and prioritisation platform.

With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, an urgent need exists for clinical support tools that identify the clinical implications associated with specific mutation events. To this end, we have developed two complementary tools for the interpretation and visualization of cancer variants, enabling researchers and clinicians to make discoveries and treatment decisions: 1) OncoKB (http://oncokb.org) is a precision oncology knowledge base that annotates the biologic and oncogenic effects as well as prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response on the basis of US Food and Drug Administration labeling, National Comprehensive Cancer Network guidelines, disease-focused expert group recommendations, and scientific literature. 2) The cBioPortal for Cancer Genomics (http://cbioportal.org) is a web-based analysis tool for the visualization and analysis of cancer variants. Through its intuitive interface it makes complex cancer genomics data easily accessible by researchers and clinicians without bioinformatics experience. It integrates information from OncoKB to enable the identification of potential driver mutations and therapeutic options. Both resources are used routinely at Memorial Sloan Kettering Cancer Center

Antibody engineering has been demonstrated as a necessary part of biologics discovery to improve the drugability. In this talk we will cover the general strategy and some case studies regarding humanization, affinity maturation and developability assessment.

The presentation covers recent advances of our engineering and applications of bispecific antibodies and engineered derivatives. New data and examples are presented that demonstrate the importance of combining suitable binders and formats to produce bsAbs with desired functionalities. We also demonstrate that large binder-format matrices can be covered by our novel FORCE technology.

Recombinant immunotoxins are antibody fragments fused to protein toxins which bind to cell-specific antigen, internalize, and undergo toxin-catalyzed cell death. Anti-CD25 recombinant immunotoxin LMB-2 bound to CD25 and showed activity in several hematologic malignancies including adult T cell leukemia (ATL) and hairy cell leukemia (HCL). Combined with chemotherapy to decrease immunogenicity, LMB-2 achieved a high complete remission (CR) rate in leukemic ATL. Recombinant anti-CD22 immunotoxin BL22 achieved CRs as a single-agent in chemoresistant HCL and an improved version Moxetumomab Pasudotox (Moxe) was FDA approved for relapsed/refractory HCL. Current efforts include combination with anti-CD20 mAb to prevent immunogenicity and improve cytotoxicity.

Elucida is developing ultra-small tumor-targeted nanoparticle drug conjugates for the treatment of cancer.  CDCs' unique properties, including their 6-7 nm size, silica core and PEG layer allow them to rapidly target and penetrate into tumors with minimal normal tissue retention – attractive qualities for payload delivery vehicles.  Preclinical studies with Elucida’s lead anti-folate receptor alpha CDC EC112002 will be presented.

A promising strategy for treating cancer is to employ a bispecific antibody that can redirect T cells to tumor cells regardless of the specificity of T cell receptors. We developed a bispecific antibody, ERY974; it targets glypican 3 (GPC3) whose expression is highly specific to many types of solid tumors, such as hepatoma and non-small cell lung carcinoma. ERY974 exerts strong anti-tumor activity against a variety of tumor models including those with a non-inflamed phenotype. In this talk, I will discuss the detailed preclinical characterization of ERY974, including the cytokine release mechanism and potential combination therapies.

Glypican 2 (GPC2) is a cell surface proteoglycan overexpressed in childhood cancer. We discover a high affinity monoclonal antibody, CT3, that specifically recognizes GPC2. CT3-derived CAR T cells regress tumors in advanced neuroblastoma mouse models, providing a strategy to improve current therapies for treating childhood cancer.

ABclonal has developed a novel monoclonal antibody (mAb) discovery platform, SMab^TM platform, based on single B cell isolation, culture, and cloning. Using universal SMab^TM platform, ABclonal can rapidly develop monoclonal antibodies from a panel of hosts including rabbit, llama, and human. This has significantly shortened the mAb screening process with greater diversity and efficiency, and allows ABclonal to deliver the best-in-class rabbit monoclonal antibodies (RmAb) to our CRO clients.

The integration of high-throughput sequencing data in antibody screening accelerates and improves discovery of novel therapeutic antibodies. Discover how you can perform efficient, integrated analysis to improve and expand your antibody candidate pool with NGS data.