Senior Scientist, Max Delbruck Center and Senior Scientific Advisor, Alithea Bio
Registration from 8am
London Heathrow Marriott Hotel
TMB and Neoantigen Congress
地點：英國，倫敦，London Heathrow Marriott Hotel
“I met leading companies/biomarker developers at one place sharing cutting edge technologies”.
“interesting mixture of topics; possibility to discuss with the attendees”
“Learned a lot from some of the talks”
2019年10月10日(四) – 關於TMB與新生抗原研究之運用
RAJIV RAJA, Director, Oncology Translational Medicine, AstraZeneca, USA
Circulating tumor DNA (ctDNA) derived from plasma offer significant promise as a tool for assessing tumor burden and antitumor response. Changes in levels of ctDNA from baseline have been shown to correlate with response to some immunotherapies. Recent studies have also shown that ctDNA could be used to measure tumor mutation burden (TMB) which could be a potential predictive biomarker for response to immunotherapies. ctDNA results from immunotherapy studies will be discussed, and opportunities and challenges with ctDNA analysis will be discussed.
CHRISTOPHE LE TOURNEAU, Head, Department of Drug Development and Innovation (D3i), Institut Curie, France
Optimising patients benefit whilst reducing toxicity risk is the ultimate goal of precision medicine in oncology. While precision medicine has always been a reality in medicine with treatments adjusted based on the clinical condition of patients, the term “precision medicine” has arisen with the advent of molecularly targeted therapies that were developed based on biomarkers that were mostly DNA alterations. Precision medicine does not apply only for molecularly targeted therapies but also for immunotherapeutics especially immune checkpoint inhibitors, for which predictive biomarkers of efficacy have been identified at the genomic level.
Morning Refreshments / Poster Presentations
Will whole genome sequencing of fresh frozen tumour material become the assay of choice for cancer molecular diagnostics?
WILL SPOONER, Commercial Programme Delivery Lead, Genomics England, UK
At the start of the 100,000 Genomes Project it became clear that formalin fixed paraffin embedded tumour material was not suitable for whole genome sequencing. An alternative “WGS friendly” fresh frozen protocol (FF-WGS) was developed and implemented as a clinical pathway in the NHS. This protocol has been used to generate a dataset of linked genome-to-health data from 15,000 cancer cases. Analysis of the dataset suggests that our FF-WGS assay that has the potential to more reliably and accurately measure cancer markers such as TMB. This talk presents these data and considers the challenges of introducing FF-WGS-based tests into clinical
trials and practice. Finally, we speculate on the mining of large FF-WGS datasets to identify the next generation of cancer biomarkers.
TMB and MSI in clinical application using comprehensive tumor profiling
MARTIN ZOCHE, Director Molecular Tumor Profiling, University Hospital Zurich, Switzerland
• Comprehensive molecular tumor profiling is standard at the University Hospital Zurich is as a diagnostic standard
procedure for all tumor patients.
• Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) analysis are integrated in the molecular report
• Patient cases will illustrate the advantages for the tumor patients
ATLAS™ - A Critical Tool in Finding True Neoantigens
PAMELA CARROLL, Senior Vice President, Scientific Strategy, Genocea Biosciences, USA
• ATLAS™ is a powerful tool that screens all candidate neoantigens for pre-existing patient-specific CD4 or CD8 responses
in an HLA agnostic assessment.
• ATLAS also identifies inhibitory peptides that may suppress tumor immunity, accelerate tumor progression and mediate
patient response to immune checkpoint blockade therapies.
• ATLAS-selected neoantigens are the basis of a vaccine, GEN-009, currently being evaluated in Phase 1/2a clinical trials. Also, ATLAS is
being applied to a personalized non-engineered T cell therapy program that targets multiple neoantigens.
Combined treatment with checkpoint blockade and Adenovirus vaccine targeting multiple neoantigens eradicates large tumors in mice
ELISA SCARSELLI, CSO, Nouscom, Italy
• Non-human Great Ape Adenoviruses (GAd) are potent vaccine vectors able to encode many neoantigens
• Vaccination synergizes with α-PD-1 in mice bearing large established tumours
• Combined treatment results in diversification of the intra-tumor T cell repertoire
Considerations and experiences from taking a fully personalized targeted cancer neoantigen DNA vaccine into the clinic
AGNETE FREDRIKSEN, President and CSO, Vaccibody, Norway
• What is the rationale to pursue development of individualized cancer vaccines and make it a viable product for the market?
• How does the vaccine format affect the immunogenicity profile of individual neoepitopes?
• Update from DIRECT-01, a clinical trial testing private cancer neoantigen based vaccines in patients with advanced cancer
Afternoon Refreshments / Poster Presentations
Tailor-made immunotherapies: Integrating non-mutated and neoantigens into highly personalized
SARAH MISSEL, Director, Translational Development, R&D Strategy and Communications, Immatics, Germany
• The role of neoantigens and non-mutated antigens in tumors with low mutational burden
• GAPVAC – Actively Personalized Vaccination in newly diagnosed glioblastoma patients – results of the clinical study
• Highly personalized Adoptive Cellular Therapy
Viral-based vaccine for cancer neoantigen vaccination
KAIDRE BENDJAMA, Project Leader, Personalized Cancer Vaccination, Transgene, France
Viral vectors constitute a promising modality for cancer vaccines. Viral vectors were used successfully to generate cancer vaccines in a number of indications using Tumor associated antigen as targets to induce a specific T cell response. The presentation will provide an overview on how Transgene uses the MVA viral strain to meet specific challenges related neoantigen vaccination from sequencing to neoepitope selection to manufacturing and QC to deliver a clinical grade product and on how these vaccines will be translated into the clinic in indications of high medical needs.
Networking Drinks Reception
GEORGE VASMATZIS, Co-director of the Biomarker Discovery Program, Associate Professor, Department of Molecular Medicine, Mayo Clinic, USA
• We observed that inter- or intrachromosomal rearrangements are present in many cancers frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis.
• Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones.
• Subsets of prostate, lung, and breast, cancers as well as some sarcomas are among those that could present neoantigens that derive from complex rearrangements
PepPipe - an immunomics workflow elucidating antigenic peptide biomarker signatures for minimal invasive diagnostics
ANDREAS WEINHAUSEL, Thematic Coordinator, Molecular Diagnostics, AIT - Austrian Institute of Technology, Austria
Autoantibody & antibody-profiles are biologically meaningful and suitable as early and minimal invasive markers using 10µl of plasma or serum. Since the immune system plays a major role in many diseases, sero-testing and immunomics analysis has a broad area of application and a high potential for diagnostics of autoimmune, cancerous, cardiologic, neurodegenerative and systemic diseases, as well as assisting biotech and pharma for selecting therapeutic targets or study off-target reactivities. PepPipe provides an entire workflow of optimised and QM qualified methods to define antigenic proteins and peptides for
serological analysis. We have developed a broad variety of assays with different multiplexing capacities to provide the entire workflow “from screening to validation” and “from proteins to peptides” to define and analyse antigenic proteins and peptides supporting clinical and therapeutic developments, and improving robust minimal invasive diagnostics.
Morning Refreshments / Poster Presentations
The promise and challenge of TMB in the clinics for immunotherapy
EUN-ANG RAIBER-MOREAU, Associate Principal Scientist, AstraZeneca, UK
Tumour mutational burden (TMB) is emerging as an important biomarker that hold promise to aid in the selection of patients for immunotherapy. TMB is defined as the total number of mutations per megabase within the coding area of the genome. TMB was initially assessed using whole exome sequencing but new studies have shown that targeted NGS panels can be used for TMB calling reducing down the costs and turn-around time. In this presentation, we will discuss the challenges of implementing TMB testing into routine clinical settings with a focus on the importance of TMB standardization and blood versus tissue TMB testing
Developing proteogenomcis platforms in cancers of high unmet clinical need
TEDD HUPP, Chair of Cancer Research, University of Edinburgh, UK
Proteogenomics platforms are being developed that can reveal the expressed cancer genome as we evolve towards personalized therapies. Our network aims to (i) define comprehensively the biological sources of cancer neoantigens; (ii) evolve algorithmic strategies for mass-spectrometry based mutation identification; (iii) identify novel genes that regulate MHC Class I production in cancers; and (vi) apply this knowledge on the mutant peptidome to form therapeutic options in cancers of high unmet clinical need.
Using Artificial Intelligence to accelerate Immunotherapy
JENS KRINGELUM, Director, Genomic Immuno Oncology, Evaxion Biotech, Denmark
• What is AI and how can it be used to predict immune responses in patients
• The use of AI driven prediction tools for design of novel immunotherapies
• Opportunities and challenges in using AI technology to drive truly personalised treatments
Application of in vitro tools that improve selection of (neo)epitopes and characterize T cell responses
ASTRID VISSER, Business Development Manager, Sanquin, The Netherlands
• Measured peptide-MHC binding / stability that improves (neo)epitope selection
• Multi-parameter FACS that efficiently detects and characterizes multiple pre-existing and induced epitope-specific
• Efficient peptide-MHC-exchange based assay that allows cross-reactivity and safety studies for peptide-MHCantibodies and TCR mimics
Personalized NeoTCR-T Cell Therapies for Solid Tumors
ALEX FRANZUSOFF, CEO, PACT Pharma
PACT Pharma is developing personalized tumor-mutation (neoantigen or neoepitope) targeted T cells tailored for each patient. Using (non-viral) precision genome engineering, a fresh collection of autologous patient T cells are reprogrammed to produce ‘native’ autologous tumor mutation-targeted T cells (neoTCR-T cells) for administration as a ‘living drug’ back to the patient. In this talk, I will discuss PACT’s development of neoTCR-T cell products exclusively for each patient, as well as the remarkable landscape of neoE-specific T cells (direct capture) in blood or TILs of patients, as well as the evolution of neoE-T cell responses in I-O trials. These developments represent a new frontier for programming fresh, autologous human T cells with ‘new tricks’ to personalize the treatment of patients with the spectrum of solid tumors.
Profiling of neo-antigens presented by cancer cells facilitate patient stratification and development of potent antitumor therapies
TIM FUGMANN, Senior Scientist, Max Delbruck Center and Senior Scientific Advisor, Alithea Bio, Switzerland
• Aberrantly expressed transcripts lead to presentation of neo antigens on cancer cells
• Aberrant expression is a common event leading to antigens shared between multiple tumors
• Such neo antigens can be targeted by adoptive T cell therapies
Chair’s Closing Remarks / Conference Close
London Heathrow Marriott Hotel
Bath Road, Harlington, Hayes, Middlesex, UB3 5AN
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