*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

  • Jason O’Rourke Associate Director – In Vivo Pharmacology, Fate Therapeutics

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

  • Hongjun Song Professor - Neuroscience, University of Pennsylvania

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 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

10:00 am Discussion/Q&A

10:30 am Morning Refreshments & Speed Networking

Enhancing Clinical Translatability of Immune Oncology Antibody-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

  • Lorenzo Galluzzi Assistant Professor – Cell Biology & Radiation Oncology, Weill Cornell Medicine

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 Discussion/Q&A

12:30 pm Roundtable Lunch & Networking

  • Shon Green Senior Director - Translational Sciences, Umoja Biopharma

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

1:30 pm MADR: Multiplex In Vivo and In Vitro Genetically Engineered Tumor Models for Immuno-Oncology Preclinical Discovery & Testing

  • Joshua Breunig Associate Professor, Cedars-Sinai Medical Center & UCLA

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

1:50 pm Bioengineered Tumor Organoids for Personalized Medicine Applications

  • Shay Soker Professor, Wake Forest School of Medicine

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

2:30 pm Discussion/Q&A

  • Lorenzo Galluzzi Assistant Professor – Cell Biology & Radiation Oncology, Weill Cornell Medicine
  • Joshua Breunig Associate Professor, Cedars-Sinai Medical Center & UCLA

3:00 pm Chair’s Closing Remarks & End of 5th PREDiCT: Tumor Models San Francisco