Improving Immunotherapy Efficacy and Safety

 

改善免疫疗法有效性及安全性

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

SUNDAY, APRIL 7

Recommended Short Course(s)*

SC4: Understanding and Modulating Tumor Microenvironment for Immunotherapy

David A. Eavarone, PhD, Associate Principal Scientist, Harbour Biomed

 

SC7: Translational Biotherapeutic Development Strategies Part 2: Analytical and Clinical Considerations

Zhiqiang An, PhD, Professor, Chemistry; Director, Texas Therapeutics Institute, University of Texas Health Science Center at Houston

Scott L. Klakamp, PhD, Senior Director & Head, Biophysics, Biologics Development Sciences, Janssen BioTherapeutics

Liming Liu, PhD, Senior Principal Scientist, Pharmacokinetics, Pharmacodynamics and Drug Metabolism (PPDM), Merck Research Laboratories

An Song, PhD, Senior Vice President, Development Sciences, Immune-Onc Therapeutics, Inc.

 

*Separate registration required.

MONDAY, APRIL 8

7:00 am Registration and Morning Coffee

EMPOWERING THE IMMUNE SYSTEM

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

Nelson BradBrad 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 Development of Pegilodecakin, a PEGylated IL-10

Oft MartinMartin Oft, MD, Senior Vice President, Preclinical and Clinical R&D, ARmo Biosciences, a Wholly Owned Subsidiary of Eli Lilly


9:40 A Multiantigen-Targeting Cytotoxic CD4+ T Cell Approach for Treating B Cell Malignancies

Zhang_BaochunBaochun 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

ADVANCES IN CHECKPOINT INHIBITORS AND IO COMBINATIONS

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

Baynes_RoyRoy 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

Curran_MichaelMichael 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

Jaen_JuanJuan C. Jaen, PhD, President, 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 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:50 Session Break

2:20 Problem-Solving Breakout Discussions

3:20 Networking Refreshment Break

PLENARY KEYNOTE SESSION

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-GandhiLeena 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

keynote-headshot-hastie-400x400Kathryn 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

7:15 End of Day

TUESDAY, APRIL 9

8:00 am Registration and Morning Coffee

NK CELLS, SWITCHABLE CAR Ts

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?

Klingemann_HansHans 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 Memory Formation in Switchable CAR T Cells

Young_TravisTravis Young, PhD, Vice President, Biologics, CALIBR

To improve the control of CAR T cells with the goal of overcoming associated toxicities and tumor resistance mechanisms, we have designed a switchable CAR T cell platform using antibody-based molecular switches. This platform enables fully tunable control of CAR-T cell activity in a universal format that can be redirected to nearly any therapeutic antigen target. Recently we’ve demonstrated how switch dosing regimen impacts memory sCAR T cell formation.

9:30 Dual-Switch CAR-NK Cells; Inducible and Targeted Anti-Tumor Efficacy with Safety

Bayle_HenriJ. 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

MITIGATING CAR T TOXICITIES

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

Kenderian_SaadSaad 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

Giavridis_TheoTheodoros 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

powell_DanielDaniel 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

CAR T FOR SOLID TUMORS, NON-VIRAL GENOME TARGETING

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

Li_ZonghaiZonghai 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

Mcginness_KathleenKathleen 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 Sponsored Presentation (Opportunity Available)

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:25 Reprogramming Human T Cell Function and Specificity with Non-Viral Genome Targeting

Roth_TheoTheodore 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

Cruz_Conrad_RussellConrad Russel Cruz, PhD, Director, Translational Research Laboratories, Center for Emerging Technologies in Immune Cell Therapy, Children’s National Hospital


5:25 End of Improving Immunotherapy Safety and Efficacy Program

5:30 Registration for Dinner Short Courses


Recommended Short Course*

SC10: CAR T-Cell Therapy for Solid Tumors

Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School

Moonsoo M. Jin, PhD, Associate Professor, Molecular Imaging Innovations Institute, Radiology, Weill Cornell Medical College

Tara Arvedson, PhD, Director, Oncology Research, Amgen

 

*Separate registration required.

* 活动内容有可能不事先告知作更动及调整。

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