3D Oncology Modeling & its Applications in IO
Synopsis
3D oncology modeling has seen a resurgence in recent times due to the versatility and cost-effectiveness they provide across a variety of cancers. This session will see speakers highlight the new capabilities that 3D models offer preclinical teams.8:50 am Chair’s Opening Remarks
8:55 am
Enhancing the Translational Confidence of T Cell–Redirection Strategies
Synopsis
Multiple methodologies exist for directing T cells to tumor cells. Checkpoint, CAR and BITE’s have generated much excitement given the range and level of function they can elicit from T-cells as well as the expansion of treatment possibilities they present for immunotherapies. This session will look to review emerging preclinical strategies for predicting, mediating and mitigating toxicities.
9:00 am Validating IO Bispecific Antibodies in Humanized Models
Synopsis
- Targets of the innate immune system are less evolutionarily conserved than the adaptive immune system, presenting challenges in pre-clinical testing
- Use of genetically engineered models and humanized mice are novel approaches to test therapeutics to these targets
- AL008 is a bi-functional antibody that antagonizes SIRPa, a myeloid checkpoint receptor, and activates Fc receptor signalling, and induces tumor regression as a monotherapy and a combination therapy in pre-clinical models
9:30 am SubQperior: A Superior Syngeneic Model System to Subcutaneous Tumor Models
Synopsis
Introducing the next generation of tumor models for immuno-oncology efficacy studies overcoming common problems experienced with subcutaneous tumor implantation
9:45 am Autologous Tumor/TIL Avatar Development to Study Patient-Specific Response to Immunotherapy
Synopsis
• Patient-matched orthotopic PDX/ TIL models were developed and validated.
• TILs with autologous tumor reactivity were successfully expanded from donor HGSOC for infusion.
• TILs co-cultured with autologous tumor cells exhibited HLA-dependent IFNγ production and activation.
• TILs in combination with anti-PD-1 significantly increased patient-matched tumor cell lysis and increased overall survival
10:15 am Morning Refreshments & Networking
11:00 am IL12-Armored CAR-T: Multi-Dimensional Data Analysis to Assess both Efficacy & Safety Considerations in an NSG Mouse Model
Synopsis
• 4th generation “Armored” CAR-T cells express a biologic payload to assist in overcoming hostile tumor microenvironments
• Many payloads, such as IL12, have potentially toxic effects when dosed systemically
• Chimera’s proprietary GOLD CAR-T cells restrict the payload delivery to the local tumor microenvironment
• We used measurements of IL12 levels and other pro-inflammatory cytokines in the blood correlated with tumor burden and time-since-tumor-clearance to compare inducible verses constitutive IL12 delivery by CAR-T cells
• Combining a temporal analysis with quantitation of both payload and effector cytokines gives a more complete picture of the benefit of GOLD-controlled delivery of IL-12 verses constitutive delivery
12:00 pm Lunch & Networking
1:00 pm The Potential of 3D Tumor Organoid Models in Testing ImmunoOncology Therapeutics
Synopsis
• Get an overview on the 3-D hydrogel system, particularly synthetic/ polymeric; PDX use in vitro; and microfluidic perfusion plates
• Discussing the incorporation of more immune components and IO aspects in our current model
1:30 pm Modeling Immune Mediated Beta Cell Destruction in Human Type 1 Diabetes With Islet Organoids
Synopsis
• Organ-immune interactions are critical and often under-appreciated and we can derive important learnings from human organoid models for autoimmune diseases, some of which might be rather helpful for the tumor immunology field
• Islet beta cell stress is a critical component of immune destruction
• We have created, an islet organoid model that allows for precise evaluation of islet stress, also via imaging, and immune attacks. The key here is the reliability and small deviations of the system, which is assured by the microfluidic device and using organoids
2:00 pm Afternoon Refreshments & Networking
2:45 pm iPSC-Derived 3D-Human Organoid Platforms for Cancer Modeling
Synopsis
• Differentiation of iPSC into 3D Human Fallopian Tube Organoids
• Generation of BRCA1mut iPSC lines
• Using Fallopian Tube Organoids to Model BRCA1mut Ovarian Cancer
• Modeling Inherited Breast Cancer Using BRCA1mut iPSC
• Generation of Barcoded iPSCs and Organoids
3:15 pm Panel Discussion: Lifting the Lid on – 3D Oncology Modeling
Synopsis
• 3D modeling and its capabilities have been somewhat of a blind spot for
preclinical and translational oncologists. In this discussion we will lift the lid on
these models to reveal what the future may hold for research teams that are
looking to embrace these technologies
• As well as the capabilities, we will also consider the short comings and the areas
that are yet to be explored
3:45 pm Chimeric Antigen Receptor T Cell Therapy: New Directions
Synopsis
- Define current challenges in CART cell therapy
- Identify new strategies to enhance CART efficacy and reduce their toxicities
- Discuss novel ways to track and image CART cells in solid and blood malignancies