8.00am Online Registration & Virtual Coffee Networking

Chair’s Opening Remarks

8:30 am Bispecific γδ-T Cell Engagers for the Treatment of Cancer

  • Paul Parren Executive VP and Head of R&D, Lava Therapeutics

Synopsis

  • Next generation bispecific antibody technology for T cell engagement
  • Widening the therapeutic window
  • Progress towards the clinic

8:50 am Challenges of Preclinical Models of Anti-Tumour Immunotherapies Utilizing Vγ9Vδ2 T Cells

Synopsis

• Explosive growth in the number of immunotherapies
• Human allogeneic Vγ9Vδ2 T lymphocytes as attractive immune cell stress sensors
• Clinical trials in humans with mixed efficacies
• Issues/Need of relevant and robust preclinical models
• Description of novel preclinical models and strategies for therapeutic improvements

9:10 am Of Mice & Men: Molecular & Functional Diversity of γδ T Cells

Synopsis

• Discuss similarities and differences between mouse and human γδ T cells
• Explore the difficulties translating from mice to men
• Discuss the innate versus adaptive γδ TCR repertoire
• Discover the role and ontogeny of human γδ T cells in early life

9:30 am The Integrin, LFA-1, Regulates the Survival of Murine Vγ6Vδ1+ IL-17- Producing γδT Cells

Synopsis

• LFA-1-deficient mice display a 20-fold increase in γδ T cells in specific tissues (lungs, uterus and spleen) due to an increase in the Vγ6Vδ1+ IL-17-producing subset
• Single cell RNA sequencing reveals enhanced expression of genes known to negatively regulate apoptosis
• LFA-1-deficient Vγ6+ γδ T cells show enhanced survival ex vivo, demonstrating that survival promotes the accumulation of this subset in LFA-1-deficient mice
• This expanded subset has the potential to influence immune responses to cancer and infection, particularly in the lungs
• By understanding the molecular control of tissue-resident γδ T cells, our findings may influence the development and optimisation of γδ T cell therapy

9:50 am Live Q&A Discussion

10:10 am Morning Break & Virtual Speed Networking

11:00 am New Insights & Perspectives in the Use of Vδ1 Anti-Tumour Effector- Functions to Develop Alternative Protocols of Adoptive Cell Immunotherapies

Synopsis

• Vδ1 T cells are more enriched at tissue sites, represent the first gamma delta T cell subset to face the development of solid tumors and are less affected by the toxicities of tumour chemotherapy
• High frequencies of Vδ1 T cells infiltrating solid tumors are associated with a better prognosis and patients’ overall survival
• Several cancers can induce an expansion of oligoclonal subsets of Vδ1 T cells that can also re-circulate in the blood stream and are endowed with high anti-tumour effector-functions
• Vδ1 T cells can be easily expanded from either peripheral blood to thymic precursors and express a peculiar repertoire of cytotoxic receptors that makes them much more efficient in their anti-tumour functions compared to Vδ2 T cells

11:20 am Co-Stimulation in Trans: Optimizing CAR Signalling in γδT Cells

Synopsis

• Stimulation in cis- vs trans-
• Co-stimulatory only CARs
• CAR signaling insight

11:40 am Novel Immunotherapy Specific for & Effective Against Immunosuppressive γδ1 T Cells

Synopsis

• γδ1 T cells possess a pro-tumorigenic capacity and are enriched in tumors such as pancretic ductal adenocarcinoma (PDA), glioblastoma, breast cancer, cholangiocarcinoma, colorectal cancer and melanoma – where they can confer resistance to checkpoint inhibitors
• We have used phage display-based selection to generate a novel, fully human IgG1 antibody, specific to both human and monkey δ1
• Our anti-Delta1 antibody, LYT-210, has high therapeutic affinity to human and monkey δ1, specifically binds δ1 and binds across many γ/δ1 pairs
• Functionally, LYT-210 potently induce the therapeutically desired ADCC/ADCP effector functions, resulting in Delta1 T cell killing
• Treating patent derived organotypic tumor spheroids (PDOTS) from multiple cancer types with LYT-210 achieves robust T cell activation

12:00 pm Exploring Vγ9Vδ2 T Cells & Receptors

Synopsis

• Discussing Vγ9Vδ2 T cells and receptors against solid cancer
• Gamma delta T cell targeting towards solid cancers
• Preclinical models to understand heterogeneity of tumors and T cell products
• Mode of action of Vγ9Vδ2 TCR targeting of tumors
• Highlighting the Mode of Action of Tumor Recognition by Vγ9Vδ2 TCRs

12:20 pm Live Q&A Discussion

12:40 pm Roundtable Discussion & Networking Lunch

12:40 pm Vg9Vd2 T cells: Translating an Infection Response to Cancer Biology

  • Christoph Baumann Principal Scientist & Cancer Biotherapeutics Project Leader, Boehringer Ingleheim

Synopsis

Roundtable Discussion

1:30 pm Vδ1 T Cell Expansion, Differentiation & Tumour Targeting

Synopsis

• Molecular cues for Vδ1 T cell expansion and differentiation
• Characterisation of “Delta One T (DOT) cells” as an expanded Vδ1 T cell product
• Recognition and targeting of haematological tumours by DOT cells
• Recognition and targeting of solid tumours by DOT cells

1:50 pm Decoding the Tumour Suppressive Immune Network in Multiple Myeloma Using Vγ9Vδ2 T Cells

Synopsis

• Vγ9Vδ2 T cells isolated from the bone marrow of patients with multiple myeloma are senescent and anergic to phosphoantigen stimulation
• They express multiple immune checkpoint (ICP) receptors that are upregulated upon ineffective phosphoantigen stimulation
• ICP upregulation is driven by intracellular pathways intersecting the TCR downstream signalling pathway
• Tumor cells and immune suppressor cells in the bone marrow express multiple (ICP ligands (ICP-L) to engage Vγ9Vδ2 T cells
• The robustness of the ICP/ICP-L network is dependent on the clinical stage
• Dual or triple ICP blockade with different combination is required to alleviate the anergy of Vγ9Vδ2 T cells in the BM of MM patients

2:10 pm Plasticity of Human γδ T-cells: Modulation by Vitamin C & TGF-β

Synopsis

• Discussing various aspects of how the effector activity of human γδ T-cells can be enhanced
• Vitamin C increases the proliferative activity, cytokine production and cytotoxicity of human Vδ2 T-cells in vitro
• Purified γδ T-cells expanded in the presence of TGF-β display enhanced cytotoxic activity
• In the presence of TGF-β, Vitamin C increases FOXP3 expression and suppressive activity of Vδ2 T-cells, and induces specific hypomethylation in the FOXP3 gene

2:30 pm Simple, Reliable, & Scalable Manufacturing Process that Overcomes the Common Challenges Faced in Manufacturing Allogeneic Human Vγ9Vδ2 γδ T Cells

Synopsis

• Discuss the recognized shortcomings of conventional platforms used for manufacturing allogeneic human Vγ9Vδ2 γδ-T cells (low cellular purity requiring additional processing steps; unpredictable and relatively low absolute cell yields; often poor cell viability; unpredictable surface and functional phenotype; etc.
• Contrast this with our manufacturing platform — beginning with a discussion of the basic biology that provides the foundation of our proprietary manufacturing approach and discuss how it overcomes the common challenges faced by other platforms
• Present data showing: 1) extremely high yields of γδ-T cells from our optimized manufacturing process; 2) γδ-T cell purity so high that we do not need an post expansion processing steps; 3) cell viability far exceeding that seen when using conventional manufacturing methods; 4) the cell surface phenotype of an effector/killer cell population
• Present data confirming the broad anti-tumour activity of our manufactured cells, both in vitro and in vivo
• Discuss our clinical trial platform(s) under development

2:50 pm Boosting γδT Cell Therapeutic Persistence

  • Marta Barisa Honorary Senior Research Fellow, Great Ormond Street Institute of Child Health, University College London

Synopsis

  • Differential expansion strategies
  • Appropriate CAR design

3:10 pm Live Q&A Discussion

3:40pm Virtual Speed Networking

4:20 pm Applications of Immunosequencing & Understanding the Role of γδ and ab T Cells in Hematology, Immuno-Oncology, & Infectious Disease Research

Synopsis

  • Principles of the immunoSEQ Technology and how it is uniquely suited to explore γδ and ab T-cell responses throughout the R&D process

 

  • The potential role of γδ T cells in response to COVID-19 and how understanding these immune responses may accelerate progress towards COVID-19 diagnostics and therapeutics

 

  • Applications of the immunoSEQ Assay focused on γδ T-cell sequencing across a variety of research areas including hematology, immuno-oncology, and infectious disease

 

  • Overview of the new immunoSEQ T-MAP COVID offering and how it is being used to accelerate COVID-19 research

Research Use Only – Not for Use in Diagnostic Procedures

4:50 pm Human Blood and Tissue Resident Vd1+ T cells; Allogeneic ‘Off-the-Shelf’ T Cell Therapy Platforms

Synopsis

  • Exploring strategies to use the unique properties of Vd1 gd T cells to generate allogeneic platforms for the treatment of solid tumours and hematologic malignancies featuring the best qualities of blood and tissue derived Vd1 T cells
  • Exploring strategies to use the unique properties of Vd1 gd T cells to improve the tumour targeting and safety profile of engineered cell therapies

5:10 pm Development of Universal Off-the-Shelf γδ T Cell-based Therapies

Synopsis

• Rationale for selecting allogeneic γδ T cells as the basis for a universal off-theshelf cellular therapy
• Mechanism of action of allogeneic γδ T cells and CAR-engineered γδ T cells
• Preclinical efficacy associated with expanded allogeneic CAR-engineered γδ T cells
• Clinical-scale manufacturing of CAR-engineered γδ T cells
• Near-future clinical studies of CAR-engineered γδ T cells

5:30 pm ACTallo®, an Off-the-Shelf Adoptive Cell Therapy Approach Using αβ TCR-transduced γδ T cells

Synopsis

• We believe that γδ T cells are ideally suited for allogenic Adoptive Cell Therapy approaches because they naturally infiltrate tumors, possess intrinsic antitumor activity and recognize target cells in an HLA/peptide independent fashion, not causing Graft-versus-Host Disease
• ACTallo® is a process developed by Immatics for the manufacture of allogeneic, offthe- shelf, TCR-engineered cellular therapies derived from healthy donors’ γδ T cells
• At the laboratory scale, Immatics has observed that its proprietary manufacturing process could generate hundreds of doses from a single donor. Immatics is currently translating these lessons into large scale solutions

5:50 pm Live Q&A Discussion

Chair’s Closing Remarks

6.10pm End of GammaDelta T Therapies Summit