Turnstone Biologics to Present Preclinical Data for Selected TIL Therapy at the 2023 American Association for Cancer Research (AACR) Annual Meeting

On April 13, 2023 Turnstone Biologics Corp, a clinical-stage biotechnology company developing next-generation immunotherapies to treat solid tumors, reported that two abstracts have been accepted for poster presentations at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, to be held in Orlando, Florida, April 14-19, 2023 (Press release, Turnstone Biologics, APR 13, 2023, View Source [SID1234630072]). The presentations include preclinical data for TIDAL-01, Turnstone’s lead tumor-infiltrating lymphocyte therapy candidate based on the selection of tumor-reactive T cells (Selected TILs), which is currently being evaluated in two Phase 1b trials, as well as data showcasing an additional strategy for tumor-reactive T cell selection.

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"We look forward to sharing preclinical data at the AACR (Free AACR Whitepaper) Annual Meeting which continue to validate the exciting potential of our next-generation Selected TILs across a wide range of solid tumors," said Stewart Abbot, Ph.D., Chief Scientific Officer, Turnstone Biologics. "These results build upon evidence from our previously published data and further demonstrate the successful expansion and significant enrichment of our TILs using innovative selection strategies for identifying tumor-reactive T cells, and support clinical advancement of TIDAL-01 and our pipeline programs."

The work reflects Turnstone’s on-going collaboration with the University of Montreal Hospital Research Centre [Centre de recherche du Centre hospitalier de l’Université de Montréal, (CRCHUM)].

Full abstracts are available through the AACR (Free AACR Whitepaper) conference website, and details of the poster presentations are as follows:

Title: TIDAL-01: A selected TIL process that enriches for neoantigen-reactive TIL in solid tumors
Session Category: Immunology
Session Title: Adoptive Cell and Natural Killer Cell Therapy
Session Date and Time: April 18, 2023, 9:00 a.m. – 12:30 p.m.
Location: Orange County Convention Center, Poster Section 22
Poster Board Number: 1
Published Abstract Number: 4049

Title: Direct selection of PD1+ CD39+ tumor-infiltrating lymphocytes (TIL) from tumor dissociates enrich for functional tumor-reactive cells
Session Category: Immunology
Session Title: Adoptive Cell and Natural Killer Cell Therapy
Session Date and Time: April 18, 2023, 9:00 a.m. – 12:30 p.m.
Location: Orange County Convention Center, Poster Section 22
Poster Board Number: 4
Published Abstract Number: 4052

Twist Bioscience Launches TCR and CAR Libraries to Enable the Development of Cell Therapies

On April 13, 2023 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported the launch of Twist T-cell Receptor (TCR), and Twist chimeric antigen receptor (CAR) Libraries (Press release, Twist Bioscience, APR 13, 2023, View Source [SID1234630071]). These new libraries provide researchers with the ability to rapidly create custom libraries that can enable the identification and development of next generation cell therapies.

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"With the dramatic increase in interest around cell and gene therapies, the addition of Twist CAR and TCR Libraries offers an important and differentiated tool to enable the development of the next generation of treatments for those suffering from a wide range of diseases," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "Twist CAR and TCR Libraries allow researchers and drug developers to fine tune these receptors to address the challenges of cell therapies, including off-target toxicity, enabling rapid advancement toward the clinic."

Twist TCR and CAR Libraries are large and diverse libraries made of up to 10,000 gene fragment combinations. This exceptional diversity enables high-throughput screening and characterization of novel and known sequence variants for therapeutic discovery. In these libraries, combinations of custom gene parts are shuffled to allow customers to test multiple elements at once, explore new combinations of variable binding regions and select candidates with the greatest therapeutic potential, accelerating the discovery phase and expediting the timeline to the clinic.

"While cell therapies have made a meaningful impact clinically, they have not yet reached their full potential," said Colin Farlow, CEO & Cofounder of Serotiny. "We partnered with Twist to accelerate progress toward our goal of engineering the next generation of cell therapies. Twist built CAR libraries of exceptional size and complexity that Serotiny utilized to discover synthetic receptors, aiming to decrease the costs and increase the effectiveness of cell therapies targeting solid tumors."

Twist TCR and CAR Libraries Production Workflow

Twist designs variations of customer selected DNA sequences. The sequences then go through the assembly process where custom gene parts are "shuffled." In TCR libraries, the alpha and beta chains are shuffled to create precise user-defined alpha and beta pairs or they can be shuffled into combinatorial pairs. In CAR libraries, variants of each domain are shuffled in a process called scaffold optimization. The variants are then cloned and sequenced. Before shipping to the customer, Twist uses next-generation sequencing to verify the entire library.

Presence at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023

Information about the Twist TCR and CAR Libraries will be available at the Twist booth at the AACR (Free AACR Whitepaper) Annual Meeting 2023, taking place April 14-19 in Orlando, Florida.

In addition, Twist will present the following posters at the conference:

"Twist pan-cancer synthetic RNA fusion control for assay development", available for viewing Sunday, April 16 1:30-5:00 PM ET
"Human anti-CD40 agonistic antibodies with enhanced FcgR engagement activate immune cell and promote anti-tumor efficacy", available for viewing Monday, April 17 9:00-12:30 PM ET
"Discovery of a potent, selective, and tumor-suppressing antibody antagonist of DKK1", available for viewing Monday, April 17 1:30-5:00 PM ET
"High-sensitivity detection of specific ultra low-frequency somatic mutations for minimal residual disease monitoring", available for viewing Wednesday, April 19 9:30-12:30 PM ET
"An end-to-end workflow for improved methylation detection", available for viewing Wednesday, April 19 9:30-12:30 PM ET

Affini-T Therapeutics Presents Preclinical Data from its Oncogenic Driver Program Targeting KRAS at the American Association for Cancer Research (AACR) Annual Meeting 2023

On April 13, 2023 Affini-T Therapeutics, Inc., a precision immunotherapy company unlocking the power of T cells against oncogenic driver mutations, reported that Loïc Vincent, Ph.D., Chief Scientific Officer and Christopher A. Klebanoff, M.D., physician-scientist at Memorial Sloan Kettering Cancer Center (MSK), who also serves as Scientific Co-founder and Advisor, Affini-T Therapeutics, are presenting data from the company’s T cell receptor (TCR) T cell therapy program targeting KRAS G12D mutations, at this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando (Press release, Affini-T Therapeutics, APR 13, 2023, View Source [SID1234630070]).

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"At Affini-T, we are targeting oncogenic drivers utilizing TCR-engineered T cells equipped with new synthetic biology elements capable of addressing some of the major obstacles in treating solid tumors, including T cell exhaustion and functional durability," said Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics. "Similar to our previously reported KRAS G12V data, our new preclinical data show a promising activity and tolerability profile in targeting KRAS G12D mutation that supports our mission to eradicate difficult to treat solid tumors with precision immunotherapies. Leveraging our platforms, TAILORTM, TUNETM and THRIVETM, we look forward to working with Dr. Klebanoff to progress our programs for patients with solid tumor cancers, including lung, colorectal and pancreatic cancer."

Oral presentation details are as follows:

Preclinical development of safe and effective T cell receptors specific for mutant KRAS G12D peptide

Abstract #1127, Session MS.CL07.01 – Immunotherapy
Session Date/Time: April 16, 3:52 pm – 4:07 pm ET
Presenting Author: Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics
Summary: T cell receptors (TCRs) directed against KRAS G12D mutant peptide/HLA-A*11:01 complex were isolated and prioritized based on specificity, functional avidity, and cytotoxicity, and were subsequently engineered into primary CD4+ and CD8+ T cells. The in vitro and in vivo preclinical data demonstrate a promising activity and tolerability profile of the KRAS G12D mutant TCR-engineered CD4+ and CD8+ T cell therapy. The study supports the planned clinical development of this novel KRAS G12D mutant TCR-engineered CD4+ and CD8+ T cell therapy for treating patients with KRAS G12D mutant / HLA-A*11:01 cancers.
Oral presentation details are as follows:

Immunogenicity and therapeutic targeting of recurrently mutated ‘public’ neoantigens

Session SY18 – Dharma Master Jiantai Symposium in Targeted Therapy: Cellular Therapies for Cancer
Session Date/Time: April 18, 12:35 pm-12:55 pm ET
Presenting Author: Christopher A. Klebanoff, M.D., Associate Member and Attending Physician, Laboratory Head, Human Oncology and Pathogenesis Program, and Member Investigator, Center for Cell Engineering at MSK; and Scientific Co-founder and Advisor, Affini-T Therapeutics
Summary: This study reports key data regarding expression of the mutant and wild type KRAS peptides by transformed and normal cells, and the discovery and characterization of a panel of patient-derived TCRs directed against the KRAS G12D mutant peptide/HLA-A*11:01 complex in vitro and in vivo.
"The findings we are presenting at AACR (Free AACR Whitepaper) 2023 are the result of outstanding scientific collaboration focused on using innovation to overcome bottlenecks that previously limited progress in the field," said Dr. Klebanoff. "I am hopeful that in future years we will see further advances resulting from our research lead to new mutation-specific TCR immunotherapies for patients with cancers that currently lack curative treatments.

Agilent Announces NGS Assay for Comprehensive Genomic Profiling (CGP) for Advancing Precision Oncology

On April 13, 2023 Agilent Technologies Inc. (NYSE: A) reported the launch of the Agilent SureSelect Cancer CGP Assay designed for somatic variant profiling for a broad range of solid tumor types (Press release, Agilent, APR 13, 2023, View Source [SID1234630069]). The pan-cancer assay design is based on an NGS panel comprising 679 genes globally curated from leading cancer databases and in partnership with key clinical cancer researchers. The assay workflow is efficient, automatable, and flexible, making tumor molecular profiling more accessible to the broad clinical research community.

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The biomarkers include key classes of somatic variants (SNVs, CNVs, indels, translocations, de novo gene fusions), along with the immuno-oncology biomarkers TMB (tumor mutational burden), and MSI (microsatellite instability) to aid clinical and translational researchers in investigating potential cancer therapeutics. Based on Agilent’s industry-leading library prep and target enrichment chemistry, this high-performance assay provides up-to-date, globally curated biomarker content for comprehensive molecular profiling of solid tumors, supports as low as 10 ng of input, and incorporates walkaway automation to improve lab efficiency and productivity. The workflow incorporates flexible data analysis options, including Alissa Interpret for tertiary analysis and reporting, customer bioinformatics pipelines, and third-party software.

"We’re pleased to commercialize the SureSelect Cancer CGP assay, which leverages our SureSelect chemistry that can accommodate a low amount of starting material so that scientists can profile more quantity-limited samples," explained Ronda Allen, Ph.D., vice president and general manager, Genomics Division at Agilent. "Library preparation and target enrichment can be automated either on the benchtop Magnis NGS prep system, which will markedly improve workflow efficiency, reducing the hands-on time from hours to only 15 minutes, or on the Bravo NGS workstation, for scaling up to 96 samples per run."

Dr. Alistair Ritchie, sequencing laboratory manager at Glasgow Precision Oncology Laboratory (GPOL), shared his experience with the assay. "The comprehensive coverage of the CGP assay means we can batch DNA from any solid tumor on a single run to streamline our workflow," he said. "Our team has come to rely on the Agilent SureSelect XT HS2 method for all our target enrichment assays. We have never used a method that gives us such reproducible results with such a low input amount."

"The release of the SureSelect Cancer CGP assay, as well as the recent acquisition of Avida Biomed, demonstrates Agilent’s commitment to developing high-performing NGS tools for an expanding oncology portfolio, accelerating the advancement of precision oncology. We are proud to partner with clinical researchers and leading cancer centers, such as Glasgow Precision Oncology Laboratory," added Allen.

Agilent is an industry leader with a continuously growing portfolio of world-class chemistries and technologies and has an established presence as a global provider and partner for biomarker analysis and companion diagnostics across the precision oncology sector.

Nucleix to Premiere Data on its EpiCheck® Lung Cancer Atlas at the 2023 American Association for Cancer Research Annual Meeting

On April 13, 2023 Nucleix, a liquid biopsy company revolutionizing cancer treatment by detecting the disease earlier, reported that it will premiere data from its early lung cancer detection discovery platform, the Nucleix EpiCheck Lung Atlas, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Event in Orlando, April 14-19 (Press release, Nucleix, APR 13, 2023, View Source [SID1234630068]). The proprietary Lung Atlas was constructed and developed as part of a multi-institutional effort to map epigenetic and genomic changes associated with early-stage lung cancer, particularly stage I disease.

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Presentations at AACR (Free AACR Whitepaper) include:

Development of a Genome-Wide Multiomic Atlas of Early-Stage Lung Cancer Enables Identification of Novel Methylation Biomarkers for Disease Detection Beyond TCGA

Session date and time: April 17 at 1:30pm ET
Machine-Learning-Based Epigenetic Detection of Early-Stage Lung Cancers Using the EpiCheck Liquid Biopsy Platform

Session date and time: April 18 at 1:30pm ET
"When lung cancer is detected early, it is more likely that patients will survive the disease," said Chris Hibberd, CEO, Nucleix. "Currently though, most patients are diagnosed with late-stage cancer, even though research has shown that five-year survival rates are up to 10 times greater when lung cancer is detected early.i Results demonstrate the strength of Nucleix’s Lung EpiCheck assay and our differentiated approach for the discovery and identification of novel biomarkers for non-invasive lung cancer screening. We are leveraging these findings to advance a new generation of Lung EpiCheck, which incorporates novel markers from the Lung Atlas and is optimized to detect minute cancer epigenetic signals with greater sensitivity. The next step is well underway as we evaluate the new assay in the Sightline Trial, a 5,000 patient multicenter study in high-risk current and former smokers."

Currently there are limited options for early lung cancer detection and only 10% of the nearly 15 million high-risk smokers recommended to receive low-dose CT imaging adhere to current guidelines.ii The Lung Atlas will aid in Nucleix’s development of the next generation of clinical assays. Nucleix’s Lung EpiCheck analyzes changes in multiple methylation markers to screen for lung cancer using a non-invasive blood sample, with a focus on testing individuals who are at high-risk based on smoking history. Lung EpiCheck has been optimized to focus on sensitivity, so that physicians have a better chance of early detection and patients have a better chance of successful treatment.

Learn more about Nucleix’s Lung EpiCheck.