Improving Immunotherapy Efficacy and Safety

Cambridge Healthtech Institute’s 5th Annual Improving Immunotherapy Efficacy and Safety conference focuses on the latest innovations, science, novel targets, and modalities being adopted to improve immunotherapy efficacy and safety. Topics include: new approaches to immunity, the tumor microenvironment, novel IO targets and engineering strategies, emerging modalities, such as NK Cells and Gamma Deltas, immune tolerance, TREGs, plus effective strategies to mitigate toxicity. Examples will come from the world of checkpoint inhibitors, adoptive T cell therapy, combinations, cancer vaccines, oncolytic viruses, and novel immunotherapy approaches.

Final Agenda


Recommended Short Course(s)*

SC3: Understanding and Modulating Tumor Microenvironment for Immunotherapy

SC6: Translational Biotherapeutic Development Strategies: Part II, Analytical and Clinical Considerations

*Separate registration required.


7:00 am Registration and Morning Coffee


8:30 Chairperson’s Opening Remarks

Laszlo Radvanyi, PhD, President and Scientific Director, Ontario Institute for Cancer Research

8:40 Therapeutic Manipulation of the Tumor Microenvironment to Enhance Response to Immunotherapy

Warner_BetofAllison Betof Warner, MD, PhD, Assistant Attending Physician, Melanoma Service, Memorial Sloan Kettering Cancer Center

Tumors are not simply collections of cancer cells; they are complex structures composed of blood vessels, immune cells, and supporting structures that interact, consume oxygen and other nutrients, and produce waste. Changing a tumor’s environment can have profound impacts on the efficacy of antitumor therapy. I will discuss the influence of microenvironmental modulators on immunobiology and our group’s approach to harness these interactions to improve therapeutic outcomes.

9:10 In vivo T Cell CRISPR Screen for Immunotherapy Target Discovery

Chen_SidiSidi Chen, PhD, Assistant Professor, Department of Genetics & Systems Biology Institute, Yale Cancer Systems Biology Center, Yale Center for Biomedical Data Science, Yale University School of Medicine

T cells have become the central focus of new cancer therapeutics. We recently performed in vivo CRISPR screens in CD8 cytotoxic T cells in tumor models of immunotherapy, which re-discovered prime immunotherapy targets such as PD-1, TIM-3, LAG3 and previously undocumented targets. Other novel immunotherapy modalities will also be discussed.

9:40 Understanding Tumor-Reactive T Cells by Repertoire and Gene Expression Analysis

Gee_MarvinMarvin Gee, PhD, Head, Target Discovery, 3T Biosciences

Although T cells can be isolated directly from tumor-infiltrating lymphocyte (TIL) specimens, recent work has called into question whether or not these T cells are necessarily tumor-reactive or perhaps specific for viral or other antigens. We've looked across tumor indications at a number of patients to identify whether or not T cell receptor clonality and TIL gene expression analysis can be used to identify tumor-reactive T cells. Using a yeast-display system, the antigen specificities of these T cell populations can be identified and linked to the tumor.

10:10 Networking Coffee Break


10:45 Chairperson’s Remarks

Laszlo Radvanyi, PhD, President and Scientific Director, Ontario Institute for Cancer Research

10:50 CAR T Cells for T Cell Malignancies

Mamonkin_MaksimMaksim Mamonkin, PhD, Assistant Professor, Center for Cell and Gene Therapy, Baylor College of Medicine

Development of effective CAR T cells targeting widely pan-T cell antigens for T cell leukemia and lymphoma has been hindered by frequent self-targeting of CAR T cells and possible induction of prolonged T cell aplasia. We developed fratricide-resistant CD5 CAR T cells that produce high anti-tumor activity in patients with refractory or relapsed T cell malignancies without eliminating healthy endogenous T cells.

11:20 Controllable CAR T Cell Therapy

Young_TravisTravis Young, PhD, Vice President, Biologics, CALIBR, A Division of Scripps Research

T cell-based therapies, including genetically engineered chimeric antigen receptor engineered T cells (CAR T cells) have produced remarkable results in clinical trials. Towards increasing the potency and safety of these therapeutics, as well as expanding them to cancers outside of the hematological space, we have defined how the biophysical characteristics of the antibody-based components of these therapies modulate the physiological response of the T cells that carry out the anti-tumor activity.

11:50 New Directions to Enhance CAR T Cell Safety

Kenderian_SaadSaad Kenderian, PhD, Assistant Professor, Medicine and Oncology, Mayo Clinic College of Medicine

Despite the unprecedented activity of CAR T cell therapy, the wider application is limited by the development of life-threatening toxicities of cytokine release syndrome and neurotoxicity. Here we will review new insights into the mechanisms of these toxicities and novel strategies to enhance CAR T cell safety.

12:20 pm Presentation to be Announced

12:50 Session Break

12:55 LUNCHEON PRESENTATION I: Uncovering Critical Receptors and Assessing Target Specificity of Biotherapeutics

Nick Brown, MSc, North American Business Development Manager, Retrogenix Limited

Cell microarray screening of plasma membrane and tethered secreted proteins that are expressed in human cells enables rapid discovery of primary 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 to aid safety assessment and provide key data to support IND submissions.

JacksonLab1:25 Luncheon Presentation II to be Announced

1:55 Session Break

2:20 Problem-Solving Breakout Discussions - View All Breakout Discussion Topics

TABLE: Combination Therapies and the Tumor Microenvironment

Moderator: Allison Betof Warner, MD, PhD, Assistant Attending Physician, Melanoma Service, Memorial Sloan Kettering Cancer Center

  • What are recent combination trials telling us about the mechanism of action of combinations in the microenvironment?
  • What role does the microbiome play and how do we harness this to improve outcomes?
  • Strategies for immune system priming and activation
  • Control of immune-related adverse events


Moderator: Saad Kenderian, PhD, Assistant Professor, Medicine and Oncology, Mayo Clinic College of Medicine

  • CART cell therapy efficacy and safety balance
  • CART cell engineering
  • CART cell application

3:20 Networking Refreshment Break


4:00 Chairperson’s Remarks

K. Dane Wittrup, PhD, J.R. Mares Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology

4:10 From Energy to Machine Learning

George-ChurchGeorge Church, PhD, Professor of Genetics, Harvard Medical School; Professor of Health Sciences and Technology, Harvard and the Massachusetts Institute of Technology (MIT)

In 1974, I adapted energy optimization methods for use in models of nucleic acids, protein and their interactions, and then for use in crystallographic refinement. In the last days of the second millennium, David Baker's team won the Critical Assessment of Structure Prediction (CASP) by an unbelievable margin. Since then, our labs exchanged 3 PhD students (Dantas, Raman, Lajoie), for Wannier from Mayo's group, Stranges from Kuhlman, and Mandell from Kortemme. We engineered new sensor proteins for metabolic engineering, essential proteins with non-standard amino acids for biocontainment, and polymerase-pore fusions for nanopore sequencing. None of this prepared us for the revolution following Gleb Kuznetsov joining our lab in 2012, joined soon by Surge Biswas, Pierce Ogden, Ethan Alley, and Sam Sinai. Together we abruptly moved to "sequence only" deep machine learning for protein design – ranging from fluorescent proteins to AAV capsids to antibodies. When combined with libraries of millions of designed gene segments from chip-synthesis and rapid testing, each design cycle can take large leaps in sequence space and function space.

4:55 The Case for Intelligent Design in Protein Engineering

spangler-jaimeJamie Spangler, PhD, Assistant Professor, Biomedical Engineering and Chemical & Biomolecular Engineering, Johns Hopkins University

Directed evolution is in its prime, and it is deepening our understanding of biological systems and empowering therapeutic design. Recent breakthroughs in structural biology, computational design, and high-dimensional data analytics afford us the unprecedented opportunity to apply molecular, structural, and computational principles to guide protein engineering, employing a so-called “intelligent design” approach. This talk will highlight how my lab harnesses this interfacial approach to overcome the deficiencies of natural proteins.

5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Co-Sponsorship Opportunity Available)

7:15 End of Day


8:00 am Registration and Morning Coffee


8:25 Chairperson’s Remarks

Lawrence Lamb, PhD, CSO, Incysus

8:30 KEYNOTE PRESENTATION: Targeting NK Cells to Treat Cancer: Individual to Off-the-Shelf Products

Miller_JeffJeffrey Miller, MD, Professor of Medicine, Deputy Director, Masonic Cancer Center, Division of Hematology, Oncology and Transplantation, University of Minnesota

NK cells can achieve complete remission in patients with refractory AML. Limitations of current NK cell strategies include single donor products, allogeneic persistence and tumor specificity. To enhance specificity, Tri-specific killer engagers can be used alone or with adoptive transfer. NK cell multi-dosing will be achieved with off-the-shelf genetically modified induced pluripotent stem cells overexpressing CD16 or CAR with an endogenous IL-15 signal to enhance persistence.

9:00 Cord-Blood Derived NK Cells

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

This presentation will discuss the technical considerations when developing cord blood NKs, alongside frequent obstacles, gene modification protocols, and potential applications.

9:30 Genetically Engineered NK Cell Lines for Treatment of Cancer and Viral Infections

Klingemann_HansHans Klingemann, MD, PhD, Vice President, Research and Development, NantKwest, Inc.

Natural killer (NK) cells obtained from blood for cellular therapy have significant limitations. The continuously proliferating NK-92 cell line (aNK) has been developed into an off-the-shelf, broadly cytotoxic NK cell therapeutic. In addition to aNK (consisting of the non-modified NK-92 cells), several variants have been engineered, expressing a high affinity antibody binding CD16 Fc-receptor (haNK) as well as CARs.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


10:45 Chairperson’s Remarks

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

10:50 Simultaneous Delivery of High-Dose Chemotherapy and Gene-Modified Chemotherapy Resistant Gamma/Delta T Cells Improve Outcomes in Primary Glioblastoma

Lamb_LawrenceLawrence Lamb, PhD, CSO, Incysus

We will discuss Drug Resistant Immunotherapy (DRI), our first-in-class approach to solid tumor cancers, a strategy combining chemotherapy-induced upregulation of tumor NKG2DL expression with simultaneous infusion of gene-modified chemotherapy resistant expanded/activated γδ T cells. Designed to target multiple tumor stress receptors at the optimal window of tumor vulnerability, DRI has shown significant promise in our initial models of glioblastoma multiforme.

11:20 BTN3A and BTN2A are New Immune-checkpoint Targeting Vg9Vd2 T Cell Functions Against Cancer Cells

Olive_DanielDaniel Olive, MD, PhD, Head Tumor Immunology, Marseillle Cancer Research Center

Vγ9Vδ2 T cell activation leads to broad functional activities against tumors. Tumor-infiltrating γδ T cells is the most significant favorable cancer-wide prognostic signature. Anti-tumoral response of Vγ9Vδ2 T cells requires sensing of phosphoantigens accumulated through binding of butyrophilin 3A(BTN3A)expressed in tumors. We identified butyrophilin 2A (BTN2A), as a requirement for BTN3A-mediated Vγ9Vδ2 T cell cytotoxicity against cancer cells.

11:50 Preclinical Evidence Supporting the Use of CAR Modified Γδ T Cells in Oncology Applications

Abbott_StewartStewart Abbot, PhD, Senior Vice President, CSO, Adicet Bio

12:20 pm Session Break

GenScript-CRO 12:25 LUNCHEON PRESENTATION I: Accelerate Antibody Drug Discovery with Single B-Cell Technology

Tina Kang, Senior Scientist, Discovery, GenScript ProBio

Antibody drug discovery is as arduous and strenuous as finding a needle in a haystack. Single B-cell technology (SBCT) is indispensable for accessing a large antibody repertoire of an immune experienced animal and the ability to interrogate each individual cells, rather than to measure the average of a cell pool. In this talk, we will 1) introduce the general approaches of SBCT 2) GenScript offerings with case study; 3) summarize the advantages of SBCT screening.

12:55 Luncheon Presentation II (Opportunity Available) or Enjoy Lunch on Your Own

1:25 Ice Cream Break in the Exhibit Hall with Poster Viewing and Poster Award


2:00 Chairperson’s Remarks

James Riley, PhD, Associate Professor, Microbiology, University of Pennsylvania

2:05 Development of the Next Generation of Cancer Vaccines: Targeting Tumor Neoantigens

Jooss_KarinKarin Jooss, PhD, Executive Vice President, Research and CSO, Gritstone Oncology, Inc.

Genetic instability in tumor cells leads to the creation of tumor-specific neoantigens. Gritstone Oncology is exploiting this by identifying a patient’s unique tumor neoantigens utilizing a proprietary neural network-based prediction model. The selected TSNA will be delivered in the context of a potent cancer vaccine consisting of an adenoviral prime and multiple self-amplifying RNA based boost vaccinations. This approach has led to high T cell titers in non-human primates and is currently being explored in humans.

2:35 Engineering Novel Targeted Cell Therapies for The Treatment of Immune Disorders

Anthony Conway, PhD, Senior Manager, Cell Therapy, Sangamo

Sangamo Therapeutics is a clinical stage genomic medicine company focused on gene therapy, cell therapy, and in vivo genome editing and gene regulation. This presentation will highlight pre-clinical data for several technology platforms and therapeutic programs.

3:05 De-Risking Antibody Lead Selection: Is Your Antibody as Specific asIntegral-Molecular_NEW You Think?

Doranz_BenjaminBenjamin Doranz, PhD, MBA, President, CEO, Integral Molecular

The Membrane Proteome Array (MPA) platform de-risks lead selection by testing biotherapeutics for specificity and off-target binding. This platform contains over 6,000 human membrane proteins, each expressed in live cells in their native conformation. In the process of testing hundreds of antibodies, we found up to 20% of antibodies exhibit off-target binding. We used our high-resolution Shotgun Mutagenesis epitope mapping platform to understand these observations and explain how some mAbs can bind completely unrelated proteins.

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

4:25 CAR T Cells for Allotransplanation

Riley_JamesJames Riley, PhD, Associate Professor, Microbiology, University of Pennsylvania

Chimeric antigen receptors (CARs) have shown remarkable ability to redirect T cells to target CD19-expressing tumours. Lessons learned from these clinical trials of adoptive T cell therapy for cancer, as well as investments made in manufacturing T cells at commercial scale, have inspired researchers to develop CARs for additional applications. Here, we explore the challenges and opportunities of using this technology to target undesired immune responses that result in transplant rejection.

4:55 Engineering Cell Therapy against Alloimmunity

Watanabe_NorihiroNorihiro Watanabe, Instructor, Center for Cell and Gene Therapy, Baylor College of Medicine

Pathologies produced by activated alloimmune T cells are a major cause of morbidity and mortality in patients following allogeneic bone marrow or solid organ transplant. We have developed engineered T cells that selectively recognize and eliminate pathogenic lymphocytes and prevent disease progression without producing systemic T cell elimination.

5:25 End of Improving Immunotherapy Efficacy and Safety

5:30 Registration for Dinner Short Courses

6:00-8:30 pm Recommended Dinner Short Course*

SC12: Emerging Applications for Gene Editing, Base Editing and RNA Editing

*Separate registration required.

* The program is subject to change without notice, due to unforeseen reason.

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