In this presentation from The Landscape of Cancer Research: Advances in Immuno-Oncology, Twist Bioscience highlights a multifaceted approach to antibody discovery targeting Dickkopf-1 (DKK1), a protein implicated in tumor progression and immune evasion. The talk, titled “Identification of Dickkopf-1 (DKK1) Antibodies Utilizing a Multi-Faceted Discovery Strategy,” outlines how Twist’s synthetic DNA and antibody libraries enabled the rapid development of high-affinity antibodies with therapeutic potential. The presentation showcases how Twist’s platform integrates high-throughput screening, precision gene synthesis, and rational design to accelerate the development of novel immunotherapies. By targeting DKK1—a promising but challenging cancer antigen—Twist demonstrates the power of its end-to-end antibody discovery workflow for advancing immuno-oncology research and supporting the development of next-generation cancer therapies.

Genomics and functional genomic approaches are needed to identify new strategies for the treatment of aggressive cancers. We use synthetic biology to build new innovative tools for editing the epigenome and driving innovation in functional genomics. Our efforts are focused on utilizing our CRISPR expertise to tackle big problems such as drug resistance in prostate cancer, leukemia, and lung cancer. We use genome-scale screens and genetic interaction mapping to identify the genetic and epigenetic causes underlying why some patients are cured and others are not by cancer therapy.  

Cancer of unknown primary (CUP) is the 6th most common cause of cancer death in Australia.  CUP has a dismal prognosis with one and 5-year survival rates of 25% and 14%, respectively. Since cancer medicine is still largely based on identifying an anatomical location of the primary cancer, CUP significantly challenges the established care paradigms. Employing precision medicine by identifying mutations that guide targeted treatments can offer an alternative cancer agnostic approach to conventional site directed chemotherapies; however, CUP patients can still be disadvantaged in this regard as access to molecularly targeted therapies through clinical trials or registered government schemes is often restricted to specific cancer types. A strong rationale therefore exists to develop better diagnostic methods for CUP to help resolve the primary origin of a patient’s tumour. Our goal is to develop and rapidly deploy clinical genomics and precision medicine for CUP patients in Australia. The SUPER-NEXT study builds upon one of Australia’s longest running clinical genomics studies: the Solving Unknown Primary Cancer (SUPER) study. SUPER-NEXT is employing clinical whole genome and transcriptome (WGTS) sequencing to measure the increased sensitivity over panel-based approaches. In addition, the use of “liquid biopsies”, targeting circulating tumour DNA in patient blood, is being tested, potentially enabling non-invasive and more rapid genomic testing. In addition to finding potentially actionable mutations in CUP tumours we are employing WGTS data for the classification of tissue of origin (TOO). Although DNA and RNA methods have both been shown to be useful in this regard, they each have their deficiencies, especially in the most challenging CUP cases where a cancer has an atypical molecular profile. We are also exploring the potential utility of DNA methylation profiling, which has also been shown to be useful for TOO prediction in CUP. Importantly, DNA methylation is highly applicable to liquid biopsy, as recently shown in the development of multi-cancer early detection (MCED) tests. One of the biggest challenges of DNA methylation analysis for clinical samples is the amount of nucleic acid needed and that samples are often suboptimal quality. The recent development of methods for enzymatic conversion of unmethylated DNA then used for next-generation sequencing combined with a large capture panel promises to enable application of DNA methylation profiling to even relatively small clinical samples such as core biopsy or plasma DNA. In this talk I will therefore describe the application of the Twist Human Methylome Panel to challenging clinical samples from patients recruited to the SUPER-NEXT study with the view to potentially employing these methods for development of TOO assays and use in the clinic.

Les outils et techniques qui permettent une détection précoce du cancer peuvent améliorer les taux de survie, car les options de traitement ont plus de chances de réussir. Les outils de dépistage précoce basés sur la biopsie liquide soulèvent toutefois des problématiques biologiques et analytiques en raison de la faible excrétion d'ADN tumoral et de la faible sensibilité analytique de nombreuses approches existantes. L'enrichissement par capture hybride des régions différentiellement méthylées, combiné à des approches de biologie computationnelle et d'apprentissage automatique, permet aux chercheurs de surmonter ces difficultés, en fournissant une analyse très efficace et uniforme des cibles d'intérêt, ce qui conduit à une identification précoce et précise des signaux de cancer.

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