Immunotherapies represent a step-change in cancer treatment, yet questions still remain around their efficacy, targeting and toxicity. Cambridge Healthtech Institute’s Improving Immunotherapy Efficacy and Safety conference details
the latest developments in immunotherapy, including established and emerging targets and modalities, new engineering strategies, combinations, biomarkers, effective preclinical models and strategies to mitigate toxicity and recent clinical developments.
Examples will come from the world of checkpoint inhibitors, adoptive T cell therapy, combinations and oncolytic viruses. We will also investigate manipulating the tumor microenvironment and emerging IO targets.
Final Agenda
MONDAY, APRIL 8
7:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Opening Remarks
Michael Curran, PhD, Associate Professor, Department of Immunology, MD Anderson Cancer Centre
8:40 Evolutionary Dynamics of the Immune Response to Cancer: Implications for Immunotherapy
Brad Nelson, PhD, Co-Director, Immunotherapy Program, BC Cancer Agency
Human cancers evolve over time and space and under various selective pressures, resulting in a high degree of intratumoral heterogeneity (clonal diversity) within individual patients. Using ovarian cancer as an example, I will review our current understanding
of the mechanisms used by the human immune system to contend with intratumoral heterogeneity and discuss immune-based strategies that might address this challenge in a clinically impactful way.
9:10 NEW: Treg Stability and Contribution to Anti-Tumor Immunity
Hye-Jung Kim, PhD., Lecturer, Immunology, Dana-Faber
9:40 A Multiantigen-Targeting Cytotoxic CD4+ T Cell Approach for Treating B Cell Malignancies
Baochun Zhang, MD, PhD, Assistant Professor of Medicine, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
Many B-cell tumors lose MHC-I expression, allowing their escape from recognition by CD8+ cytotoxic T-lymphocytes (CTLs). CD19-targeted chimeric antigen receptor (CAR)-T cell therapy bypasses the need of MHC-mediated recognition but produces durable remissions
in less than half of treated patients. Here, we present a novel approach for generating CD4+ CTLs for targeting B-cell malignancies through a wide range of endogenous tumor antigens.
10:10 Networking Coffee Break (Harbor & Mezzanine Level)
10:45 Chairperson’s Remarks
Brad Nelson, PhD, Co-Director, Immunotherapy Program, BC Cancer Agency
10:50 KEYNOTE PRESENTATION: PD-1 Antibodies Are Transforming Cancer Treatment Both as Mono and Combination Therapy
Roy Baynes, MD, PhD, Senior
Vice President, Global Clinical Development & CMO, Merck Research Labs
Pembrolizumab was initially studied in a known immune responsive cancer – melanoma. A high response rate prompted exploration of addressable malignancies. A big data enabled, biologically informed phase 2 screening program was conducted across some
30 major malignancies. Monotherapy activity is being progressively defined across lines of therapy by tumor type and also in histology agnostic biomarker informed populations. Precision medicine tools have been used to explore potential resistance
biology thereby informing combination therapy choices and development. A number of effective combinations have already been identified.
11:20 Best-in-Class PD-1 Pathway Blockade with Efficacy against Cold Tumors
Michael Curran,
PhD, Associate Professor, Department of Immunology, MD Anderson Cancer Centre
To address the therapeutic limitations of both PD-1 and PD-L1 blockade, we have developed novel, fully human antibodies which block binding of both PD-ligands to PD-1, as well as of PD-L1 to B7-1. The in vitro efficacy
of these therapeutics equals or exceeds that of pembrolizumab; however, when armed with effector function in vivo, these antibodies can regress both PD-1 sensitive “hot” and PD-1 resistant “cold”
syngeneic tumors.
11:50 Third-Generation Immune Checkpoint Inhibitors and Development of AB154, a Clinical-Stage TIGIT Antibody
Joanne B.L. Tan, PhD, Research Fellow, Arcus Biosciences, Inc.
TIGIT and DNAM-1 (CD226), expressed on lymphocytes, compete for intra-tumoral ligand CD155. TIGIT induces immune suppression, whereas DNAM-1 mediates immune activation. AB154 is a sub-nanomolar TIGIT mAb that activates T and NK cell function, as shown
in multiple in vitro assays. A flow cytometry-based assay that quantifies TIGIT occupancy by AB154 in blood is being utilized to guide dose selection in the ongoing dose escalation clinical study in cancer patients.
12:20 pm Industrializing IO Therapeutic Discovery Platforms: Multispecifics, Engineered TCRs and CARs
Andrew
Lynch, PhD, Scientific Consultant, Biologics, Genedata
Novel classes of bio-molecules are currently evaluated for their use in cancer immunotherapy. Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, non-Ig scaffolds, chimeric antigen receptors (CARs), engineered TCRs and TCR-based bispecific
constructs promise significant advantages. However, these highly engineered molecules pose new challenges in design, engineering, cloning, expression, purification, and analytics. We present an infrastructure that addresses these challenges and
enables the industrialization of these various novel therapeutic platforms.
12:50 NEW: New Mechanistic Insights into the Function of anti-CTLA-4 therapy
Dhan Chand, PhD., Senior Scientist, Agenus Inc
1:50 Session Break
2:20 Problem-Solving Breakout Discussions - Click here for details(Commonwealth
Hall)
3:20 Networking Refreshment Break (Harbor & Mezzanine Level)
4:00 Chairperson’s Remarks
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
PLENARY KEYNOTE SPEAKER
4:10 Vision for How Immunotherapy Will Shape Future of Cancer Care
Leena Gandhi, MD, PhD, Vice President, Immuno-Oncology Medical Development, Lilly Oncology
Immunotherapy is considered by many as a pillar of cancer care today, but in many ways we have only scratched the surface. Our knowledge and understanding of the complexities of immunotherapy and its mechanisms continue to evolve. The future of cancer
care will be defined by our ability to systematically identify and implement opportunities for combination therapy to improve and standardize patient response.
YOUNG SCIENTIST KEYNOTE
4:55 The Lassa Virus Glycoprotein: Stopping a Moving Target
Kathryn Hastie, PhD, Staff Scientist,
Immunology and Microbiology, The Scripps Research Institute
Lassa virus causes ~5000 deaths from viral hemorrhagic fever every year in West Africa. The trimeric surface glycoprotein, termed GPC, is critical for infection, is the target for neutralizing antibodies, and a major component of vaccines. Structural
analysis of Lassa GPC bound to antibodies from human survivors reveals a major Achilles heel for the virus and provides the needed template for development of immunotherapeutics and improved vaccines.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:15 End of Day
TUESDAY, APRIL 9
8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:25 Chairperson’s Remarks
Saad J. Kenderian, PhD, Assistant Professor, Medicine and Oncology, Mayo Clinic College of Medicine
8:30 NK Cells: Growing up to Become Safe and Efficacious Cellular Therapeutics?
Hans
Klingemann, MD, PhD, Vice President, Research and Development, NantKwest, Inc.
The continuously proliferating NK-92® cell line has been developed into an off-the-shelf, broadly cytotoxic NK cell therapeutic platform. aNK and haNK® have completed Phase I studies, while HER2 taNK® for glioma is currently accruing
patients. Further genetic modifications of the haNK platform include additional CARs as well as homing receptors and molecules that can positively affect the tumor microenvironment.
9:00 Enhancing the Efficacy of T Cell-Based Immunotherapy Through Fucosylation
Gheath Al-Atrash, DO, PhD., Associate Professor of Medicine, Section of Transplant Immunology, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center,
The homing of adoptively transferred cytotoxic T lymphocytes (CTL) to tumor tissue is a major limiting factor to the efficacy of adoptive cellular therapy (ACT) for cancer. This challenge may be overcome through fucosylation, a process whereby
fucosyltransferases (FTs) add fucose groups to cell surface glycoproteins. Ex vivo fucosylation enhances CTL homing to malignant bone marrow and solid tumor tissue and appears promising in improving the efficacy of ACT.
9:30 Dual-Switch CAR-NK Cells; Inducible and Targeted Anti-Tumor Efficacy with Safety
J. Henri Bayle, PhD, Director of Molecular Biology, Research and Development, Bellicum Pharmaceuticals
Natural Killer (NK) lymphocytes possess innate anti-tumor activity useful as an allogeneic CAR cell therapy with reduced GvHD risk relative to alpha beta T cells. To overcome poor NK cell expansion in vivo, we
utilized a molecular switch that relies on rimiducid-directed dimerization of inducible MyD88/CD40 (iMC) to control cell proliferation and cytotoxicity in vitro and in vivo.
Moreover, rapamycin-inducible Caspase-9 (iRC9) provided an orthogonally regulated safety switch.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
10:45 Chairperson’s Remarks
Kathleen McGinness, PhD, Senior Director, Platform Technologies, Unum Therapeutics
10:50 Novel Strategies to Mitigate Toxicities after Chimeric Antigen Receptor T Cell Therapy
Saad
J. Kenderian, PhD, Assistant Professor, Medicine and Oncology, Mayo Clinic College of Medicine
Despite the impressive responses after chimeric antigen receptor T (CAR T) cells in hematological malignancies, their application is limited by the development of cytokine release syndrome (CRS). The lack of relevant preclinical models for CRS
after CAR T cell therapy is a significant limitation for the development interventions to treat or prevent CRS. In this presentation, we will review relevant preclinical models of human CRS after CART cell therapy and efforts to develop and
optimize preventative strategies.
11:20 The Myeloid System in Cytokine Release Syndrome
Theodoros Giavridis, PhD, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center
We recently described the first mouse model for Cytokine Release Syndrome (CRS) elicited by anti-CD19 CAR T cell therapy, which recapitulates multiple aspects of clinical CRS. In this model we established that CRS is the result of a tripartite
interaction between CAR T cells, macrophages and the tumor microenvironment. Novel insights into the interplay between the actors of CRS will inform future considerations for CAR T cell therapy.
11:50 Next Generation Approaches for Increased Safety and Efficacy of CAR T Cells
Daniel J. Powell Jr., PhD, Associate Professor of Pathology and Laboratory Medicine, University of Pennsylvania
T cells engineered to express chimeric antigen receptors can mediate durable cancer regression in some patients with certain forms of cancer but safety and durability issues exist and the lack of efficacy in other cancer types is yet to be resolved.
I will discuss the use of modified CAR T cells approaches that allow for quantitative and qualitative control of T cell activity to address safety concerns, as well as the provision of accessory molecules that either boost efficacy or limit
CAR-associated toxicities.
12:20 pm Luncheon Presentation I: Target Specificity Screening of CAR T Cells Using Human Cell Microarray Technology
Alex Kelly, US Business Development Manager, Retrogenix Limited
Human cell microarray screening enables the discovery of both primary cell surface receptors as well as potential off-targets for a variety of biologics including: peptides, antibodies, proteins, CAR T and other cell therapies. Case studies will
demonstrate the utility of the technology in identifying novel, druggable targets as well as in specificity screening for antibodies, scFvs and CAR T cells to aid safety assessment and provide key data to support IND submissions.
12:50 Luncheon Presentation II: (Sponsorship Opportunity Available)
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
2:00 Chairperson’s Remarks
Daniel J. Powell Jr., PhD, Associate Professor of Pathology and Laboratory Medicine, University of Pennsylvania
2:05 Development of CAR-T Cell Therapeutics for Solid Tumor
Zonghai Li, MD, PhD, CSO and CSO, CARSgen
Great success has been made in CAR-T cell therapeutics for the treatment of blood cancer such as acute lymphoblastic leukemia while rare improvement has been made for solid tumor treatment. In this talk, we will summarize the current global progress
of CAR-T cell therapeutics for solid tumor and share the thoughts and strategies of CARsgen to develop CAR-T cell therapeutics for the treatment of solid tumor.
2:35 Bolt-On Transgenes Improve Engineered T Cell Function in Solid Tumor
Kathleen McGinness, PhD, Senior Director, Platform Technologies, Unum Therapeutics
The immunosuppressive features within solid tumors present unique challenges to the success of engineered T cell therapies. We have employed a “bolt-on” strategy to overcome key immunosuppressive mechanisms by co-expressing over 100
different novel transgenes in T cells bearing chimeric receptors. We have identified several bolt-on transgenes that modulate T cell metabolism or costimulation and impart enhanced function to chimeric receptor T cells in preclinical models
of solid tumor malignancies.
3:05 UTG-4D; Developing the Most Rapid Patient Tumor Model in vitro
Prabuddha Kundu, PhD, Co-Founder & Managing Director, Premas Biotech Pvt Ltd
UTG-4D, universal tissueoid generator, is the most rapid in vitro representation of the in vivo patient tumors. We have developed scaffolds for growing patient samples or tumor cell lines, or cell lines and converting them into rapidly growing
3D tissueoid models, which can be studied, dosed and therapeutic determination can be performed. Hundred’s of tissueoids have been grown with >90% success rates. The model device scaffolds enable rapid growth, within 24-48 hrs reproducibly.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:25 Reprogramming Human T Cell Function and Specificity with Non-Viral Genome Targeting
Theodore Roth, MD, PhD Student, Department of Microbiology and Immunology, University of California
Cellular therapies using human T cells are opening new chapters in cancer and autoimmune disease therapy. These living drugs can be genetically engineered to acquire new therapeutic functions. However, current methods to insert new genetic material
into human T cells require viral vectors, slowing research and hindering therapeutic development. We have developed a non-viral methodology for the targeted integration of large DNA sequences in human T cells that has enabled rapid therapeutic
reprogramming of T cell function and specificity.
4:55 Cell Therapies for HIV
Conrad Russel Cruz, PhD, Director, Translational Research Laboratories, Center for Emerging Technologies in Immune Cell Therapy, Children’s National Hospital
Antiretroviral therapy (ART) in HIV cannot cure infection: it is unable to eliminate HIV residing in latent reservoirs. Promising strategies involve the use of latency reversing agents which reactivate HIV out of latency; so far, however, most
of these approaches have shown limited efficacy. We propose a strategy based off expanding HIV-specific T cells ex vivo, and subsequent adoptive T cell transfer of these cells.
5:25 End of Improving Immunotherapy Safety and Efficacy Program
5:30 Registration for Dinner Short Courses (Commonwealth Hall)