*All Times Shown in PST
8:30 am Morning Networking
8:55 am Chair’s Opening Remarks
Establishing Success in Preclinical Development of Cell Therapy Products for I/O Applications
9:00 am In Vivo Screens in Mouse Tumor Models Treated with Pools of Edited CAR-T Cells to Identify the Next Generation of iPSC Derived Immunotherapies for Cancer
Synopsis
- Introduction to Fate’s iPSC Derived Immunotherapy Platform
- Novel multiplexed approach to generate pools of engineered CAR-T clones with different edits for combinatorial testing in vitro and in vivo
- Using genomics to screen pools of edited CAR-T in mouse tumor models to identify winning clones with specific edits
9:20 am A Patient-Derived Glioblastoma Organoid Model for Testing Personized Treatment Strategies
Synopsis
- A simple patient-derived glioblastoma organoid model and biobank that recapitulates inter- and intra-tumoral heterogeneity
- Testing personized drug treatment of strategy based on mutation and gene expression characteristics of the tumor
- Application of the glioblastoma organoid model for CAR-T treatment testing
9:40 am Using Humanized Models to Improve Translational Success for In Vivo Efficacy Studies of Tumors
Synopsis
- Introduction of target-humanized mouse models including IO target, cytokine and cytokine receptor humanized mouse models for antibodies, bispecific and combination therapies used in immuno-oncology
- Discussion of using B-NDG and second generation B-NDG based immune system reconstitution mouse models as tumor models in different therapeutic modalities including antibody and cell therapy
10:10 am Discussion/Q&A
10:40 am Morning Refreshments & Speed Networking
Enhancing Clinical Translatability of Immune Oncology Cell-Based Strategies
11:30 am SCC VII as a Novel Syngeneic Tumor Model to Assess Immune Checkpoint Blockade Resistance and CD4+ T Cell Help for CD8+ Cytotoxic T Lymphocytes
Synopsis
- Strategies for neoantigen identification rely on potential epitopes for only CD8+ T cells based on prediction algorithms despite functional cooperation between these cells and the CD4+ T cell subset is necessary for optimal cell-mediated immunity
- Using SCC VII as a poorly-immunogenic tumor model, which resembles human head and neck squamous cell carcinoma (HNSCC) in several key features, we have applied a novel functional approach to identify the subset of expressed mutations targeted as neoantigens by natural CD4+
and CD8+ T cell responses - A single mutation recognized by both subsets is capable of eradicating established, immune checkpoint blockade resistant tumors in the setting of therapeutic vaccination provided the relevant epitopes are physically linked
11:50 am MPA/DMBA-Driven Mammary Carcinomas as a Model of Luminal B Breast Cancer
Synopsis
- Hormone receptor (HR)+ breast cancer (BC) causes most BC-related deaths, calling for improved therapeutic approaches. Despite expectations, immune checkpoint blockers (ICBs) are poorly active in
patients with HR+ BC, in part reflecting the lack of preclinical models that recapitulate disease progression in immunocompetent hosts - We demonstrate that mammary tumors driven by medroxyprogesterone acetate (M) and 7,12-dimethylbenz[a]anthracene (D) recapitulate several key features of human luminal B HR+HER2- BC, including limited immune infiltration poor sensitivity to ICBs
- Moreover, M/D-driven oncogenesis is accelerated by immune defects, demonstrating that M/D-driven tumors are under immunosurveillance
12:10 pm Preclinical Evaluation of NKX019, a CD19-targeting CAR NK Cell
Synopsis
- NKX019 is a highly potent CD19-directed CAR NK cell therapy with specific cytotoxic activity against CD19+ B-ALL tumors
- NKX019 displays enhanced in vitro expansion and longer in vivo half-life than non-engineered NK cells
- NKX019 exhibits advantages compared to CAR19+ T cells including faster cytotoxic kinetics and limited production of cytokines associated with CRS
12:30 pm Discussion/Q&A
1:00 pm Roundtable Lunch & Networking
Synopsis
Roundtable discussion around the No One Size Fits All Approach – Choosing the Right Preclinical Model for the Right I/O Question
Expanding the Complexity of Pre-Clinical Modelling through Next Generation Platforms
2:00 pm MADR: Multiplex In Vivo and In Vitro Genetically Engineered Tumor Models for Immuno-Oncology Preclinical Discovery & Testing
Synopsis
- Using mosaic analysis with dual recombinase-mediated cassette exchange (MADR) to generate “personalized” tumor subtypes
- Diversifying the use of MADR for the generation of autochthonous in vivo modelling, syngeneic modelling, and multiplex organoid modelling of tumors
- Employing MADR as preclinical platforms for immuno-oncology testing and discovery
2:20 pm Bioengineered Tumor Organoids for Personalized Medicine Applications
Synopsis
- Immunotherapy have been welcomed as a significant advance in the management of multiple types of cancer, however some patients may be innately unresponsive or acquire resistance over the course of treatment
- Reconstructing the patient’s own tumor in vitro, in the form of tumor organoids containing tumor cells along with associated stroma
- Patient-specific tumor organoids have the potential not only to support personalized medicine decisions but also uncover mechanism of therapy resistance