Increased understanding of tumor immune biology, as well as advances in genetic engineering, cell culture, and delivery, have quickly positioned adoptive cell-based approaches as the next wave of successful immunotherapies, with remarkable efficacy already
demonstrated in some trials. However, due to severe side effects of first-generation agents, developers are now working on improved T cell and a suite of NK cell therapies to join the ranks of already approved I/O therapies.
Cambridge Healthtech Institute’s 2nd Annual Adoptive Cell-Based Cancer Immunotherapy symposium convenes an interdisciplinary collection of cancer researchers, drug developers, and technology providers to discuss current challenges, emerging approaches,
and updates on T and NK cell-based cancer immunotherapies in the clinic.
Final Agenda
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Thursday, March 14
7:00 am Registration Open and Morning Coffee (Continental Foyer)
8:55 Chairperson’s Opening Remarks
Dean Anthony Lee, MD, PhD, Director, Cellular Therapy and Cancer Immunology Program, Nationwide Children’s Hospital; DiMarco Family Endowed Chair in Cell-Based Therapy, Professor, Pediatrics, The Ohio State University Comprehensive Cancer Center
9:00 New Approaches for Engineering Primary NK Cells
Dean Anthony Lee, MD, PhD, Director, Cellular Therapy
and Cancer Immunology Program, Nationwide Children’s Hospital; DiMarco Family Endowed Chair in Cell-Based Therapy, Professor, Pediatrics, The Ohio State University Comprehensive Cancer Center
NK cell adoptive immunotherapy is rapidly gaining clinical traction through advances in isolation, propagation, and donor selection that are distinct from T cell methodologies. Similarly, applying T cell genetic manipulation methods has been problematic
for NK cells, and therefore requires novel approaches if we are to build on the recent manufacturing successes. Several new advances have resolved this longstanding hurdle, including novel vector pseudotypes, stealth ribonucleoproteins, and epigenetic
remodeling.
9:30 Expression of Recombinant FcRs by NK Cells to Enhance the Efficacy of Tumor-Targeting Antibodies
Bruce Walcheck, PhD, Professor, Immunology, Department of Veterinary and Biomedical
Sciences, University of Minnesota
We have engineered NK cells expressing novel recombinant Fc receptors that bind tumor-targeting mAbs with high affinity to induce robust antibody-dependent cell-mediated cytotoxicity. By this approach, NK cells can be modified with diverse and switchable
targeting elements for various malignancies.
10:00 SPEAKER CHANGE: Cancer Treatment with aNK (NK-92) – Coming of Age
Hans Klingemann, MD, PhD, Vice President, Research and Development, NantKwest,
Inc.
The continuously growing, highly cytotoxic NK-92 cells have been genetically engineered to express a high-affinity FcR for ADCC, various CARs, as well as homing receptors and mediators to counteract the inhibitory tumor microenvironment. The cells
represent the only truly off-the-shelf NK cell product. NK-92 cells have completed a number of Phase I studies and their safety has been confirmed. Combination studies with other immunotherapeutics are in progress.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 NKTR-255: Accessing the Immunotherapeutic Potential of IL-15 for NK Cell Therapies
Saul Kivimäe, PhD, Senior Scientist & Lead, in vivo Pharmacology Function, Nektar
Therapeutics
IL-15 has long been recognized as a potential immunotherapeutic agent. Exploiting this potential has been challenging due to poor pharmacokinetic properties of IL-15. NKTR-255 is an IL-15 pathway agonist that shows favorable pharmacological characteristics
and sustains pathway activation while retaining high affinity IL-15Rα binding. NKTR-255 treatment expands and prolongs activation of NK and CD8 memory T cells. NK cell-dependent anti-tumor efficacy is demonstrated in NKTR-255 treated mouse
tumor models.
11:45 Discovering Novel Therapeutic Antibody to Modulate NK Cell Activity for Cancer Immunotherapy
Zhengmao Ye, PhD, Biochemical and Cellular Pharmacology, Genentech
Natural Killer cell is a critical immune cell subset mediating tumor killing. In this presentation, I discuss a drug discovery project targeting a cell surface protein that mediates the suppression of NK and CD8+ T cell activity. I discuss the functional
assay development/antibody screening strategy for lead identification as well as antibody lead pharmacological characterization and MOA elucidation.
12:15 pm Enjoy Lunch on Your Own
1:55 Chairperson’s Remarks
Christopher W. Helsen, MSc, PhD, Director, R&D and Head, Platform Development, Triumvira Immunologics, Inc.
2:00 Combining Adoptive Cell Therapy With Oncolytic Vaccines for Treatment of Solid Tumors
Yonghong Wan, MD, Professor, Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, Cancer Division,
McMaster University
To achieve sustained regression of solid tumors, adoptive T cell therapy must be combined with other approaches that can simultaneously stimulate T cell expansion, recruit T cells into the tumor, overcome tumor-mediated immunosuppression and broaden
spectrum of T cell specificity. We present our preclinical observations that oncolytic virus vaccines can serve as such a platform to synergize adoptive T cell therapy.
2:30 Development of a CD19-TAC Therapy for a First-in-Human Phase I Study
Christopher W. Helsen, MSc, PhD, Director, R&D and Head, Platform Development, Triumvira
Immunologics, Inc.
We are developing T cell therapies based on the chimeric TAC cell receptor that facilitates selective tumor targeting and T cell activation via the recruitment of the endogenous T cell receptor. These therapies lead to effective and – unlike
CAR – controlled anti-tumor responses in preclinical models of cancer. We discuss the unique biological attributes of TAC and lead candidate TAC01-CD19 that is expected to enter clinical testing in 2019.
3:00 Engineering Next-Generation CAR-T Cells for Cancer Immunotherapy
Yvonne Y. Chen, PhD, Assistant Professor, Department of Chemical
and Biomolecular Engineering, University of California, Los Angeles
Adoptive T cell therapy offers a new cancer treatment paradigm, but a number of challenges remain to be addressed. Here, I discuss engineering solutions developed to overcome clinically observed obstacles such as antigen escape, immunosuppression,
and imperfect tumor specificity.
3:30 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall
4:15 Targeting Chemokine Receptor ACKR3 in Glioblastoma to Activate Immune Responses
Nicole Salazar
Velmeshev, PhD, Assistant Professor, Department of Biology, San Francisco State University
We used hydrodynamic gene transfer to express a chimeric single chain antibody targeting the chemokine receptor ACKR3 in vivo. Antibody-mediated targeting of ACKR3 both alone and in combination with temozolomide enhanced the activation
of innate immune cells to reduce tumor burden in mouse models of glioblastoma. doi:10.1016/j.ymthe.2018.02.030.
4:45 How to Build a Cancer Eating Machine: Chimeric Antigen Receptors that Trigger Phagocytosis
Adam P. Williamson, PhD, Postdoctoral Scholar, Ron Vale Lab, Cellular and Molecular
Pharmacology, University of California, San Francisco
The clinical success of chimeric antigen receptors that program T cells to kill cancer (CAR-Ts) highlights the power of engineering immunity. To apply a similar strategy to other immune cell lineages, we engineered chimeric antigen receptors for phagocytosis
(CAR-Ps). CAR-Ps trigger antigen-specific engulfment of synthetic targets, cancer cell bites, and whole cancer cells. Finally, CAR-P macrophages are able to limit cancer cell growth in a co-culture assay.
5:15 PANEL DISCUSSION: Patient-Centric Approaches Drive Next-Generation Receptor Discovery
Moderator:
Christopher W. Helsen, MSc, PhD, Director, R&D and Head, Platform Development, Triumvira Immunologics, Inc.
Panelists:
Yvonne Y. Chen, PhD, Assistant Professor, Department of Chemical
and Biomolecular Engineering, University of California, Los Angeles
Nicole Salazar
Velmeshev, PhD, Assistant Professor, Department of Biology, San Francisco State University
Yonghong Wan, MD, Professor, Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, Cancer Division, McMaster University
Adam P. Williamson, PhD, Postdoctoral Scholar, Ron Vale Lab, Cellular and Molecular
Pharmacology, University of California, San Francisco
Current cancer immunotherapies in advanced stages of development are clustered around similar targets. This panel shares insights for discovering new target spaces, engineering novel antigen receptors, and validating leads for promising cancer-beating
patient-centric immunotherapies.
5:45 Reception in the Exhibit Hall with Poster Viewing
6:45 Close of Day
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Friday, March 15
8:00 am Registration Open and Morning Coffee (Continental Foyer)
8:25 Chairperson’s Remarks
Adrian Bot, MD, PhD, Vice President, Translational Sciences, Kite, a Gilead Company
8:30 High-Dimensional Profiling of Human Antigen-Specific T Cells: Asking T Cells What They “See” in Cancer
Yannick Simoni, PhD, Research Fellow, Vaccine and Infectious
Disease Division, Fred Hutchinson Cancer Research Center
The utility of high-dimensional mass cytometry analysis together with rapidly evolving computational analysis tools will be discussed. For T cell antigen specificity, this analysis can be performed in conjunction with a highly multiplexed method based
on peptide-MHC tetramers. Application of these approaches to identify and phenotypically profile virus and cancer-specific T cells will be described. In addition to the possibility of finding novel therapeutic targets, a long-term goal of this
work is to discover more accurate biomarkers of clinical outcomes.
9:00 Generation of Engineered Pluripotent Cell-Derived T Cells as a Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy
Bahram (Bob) Valamehr, PhD, MBA, Chief Development Officer, Fate Therapeutics,
Inc.
I describe the creation of a universal CAR-T cell completely absent of TCR expression from renewable master pluripotent cell line, and how this reduces cost and improves patient accessibility through a true off-the-shelf approach. Additionally, I
discuss i) engineering CAR into the TRAC locus for improved product quality and efficacy; ii) targeting antigen escape through a secondary antibody-dependent mechanism; and iii) development of a cellular platform to enable multiplex engineering
in a single cell.
9:30 Single-Cell Optical Analyses for the Characterization and Development of Immunomodulatory Therapies
Andrea Pomerantz, PhD, Investigator III, Microscopy and Biophotonics (MiBs), Analytical Sciences and Imaging, Novartis Institutes for BioMedical Research, Inc.
In support of the development of new immunomodulatory therapies at NIBR, we are implementing microfluidic and confocal imaging approaches for interrogating single immune cell / target cell interaction dynamics. We have also developed single-cell imaging
flow cytometry assays for CAR-T cell therapies in order to gain a detailed understanding of factors driving the safety and efficacy of these transformative therapeutics.
10:00 Functional Capacity of Immune Cells as Measured by Single Cell Proteomics Predicts Clinical
Outcome Across IO Therapies
Will Singleterry, Director, Business Development, Isoplexis
Using single cell proteomics to measure the functional capacity or ‘fitness’ of immune cells has correlated with and been predictive of clinical outcome in CAR-T, TIL, Cancer Vaccine and Checkpoint Inhibitor therapy. This talk
will review several of these data sets and discuss applications of IsoPlexis’ single cell technology
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 FEATURED PRESENTATION: High-Resolution Characterization of CAR-T Cell “Fitness” to Aid Process Optimizations and Clinical Development
Adrian Bot, MD, PhD, Vice President, Translational Medicine, Kite, a Gilead Company
A major advantage of T cell products based on primary lymphocytes is their composition, comprising multiple subsets that may complement each other functionally towards mediating clinical outcomes. Based on a range of methods including single cell
analysis, we are advancing a systematic approach to characterize product T cell fitness that integrates three key attributes: their intrinsic expansion capability, polyfunctionality, and dose of specialized cells in the product infusion bag.
11:45 Single Cell Mass Cytometry and AI-Guided Analysis to Predict Therapeutic Response and Monitor and Direct Clinical Trials
Carsten Krieg, PhD, Assistant Professor of Immunology, Microbiology & Immunology and Dermatology, Medical University
of South Carolina
Immunotherapy has revolutionized oncology but not everyone responds to therapy or relapses under therapy. We developed a workflow based on high-dimensional single cell mass cytometry combined with augmented intelligence (AI)-supported bioinformatics
to analyze liquid blood biopsies to a) predict immune response to immunotherapy and b) monitor and direct clinical trials. The generated cellular maps, so-called “immune instagrams”, might help in stratifying patients prior to
immunotherapy, choosing the right therapeutic combination, and supporting clinical trial decisions.
12:15 pm Circulating T Cell Subpopulations Correlate with Immune Responses at the Tumor Site and Clinical Response to PD1 Inhibition in Non-Small Cell Lung Cancer
Nataly Manjarrez-Orduño, PhD, Clinical Mechanisms Lead, Bristol-Myers Squibb
Analysis of peripheral blood of cancer patients showed that peripheral T cell subpopulations inform about the state of the anti-tumor immune response and identify potential blood biomarkers of clinical response to checkpoint inhibitors in melanoma
and NSCLC.
12:45 Close of Symposium
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