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.

Monday, August 31

IMPROVING IMMUNOTHERAPY OUTCOMES AND TARGET IDENTIFICATION

Allison Betof Warner, MD, PhD, Assistant Attending Physician, 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.

9:25 am

In vivo T Cell CRISPR Screen for Immunotherapy Target Discovery

Sidi Chen, PhD, Assistant Professor, Department of Genetics and Systems Biology Institute, Yale University; Member, Yale Cancer Center and the Yale Stem Cell Center

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 rediscovered prime immunotherapy targets, such as PD-1, TIM-3, LAG3, and previously undocumented targets. Other novel immunotherapy modalities will also be discussed.

Prabuddha Kundu, PhD, Co-founder and Managing Director, Premas Biotech Pvt Ltd.

Evaluation of a new chemical/biological entities (NCE/NBE) in tumor targeting therapies takes 5-12 years for development while only a few candidates reach clinics. One bottleneck is the absence of a reliable human model with an intact tumor micro-environment & data consistency. AXTEX-4D™ seals this gap and offer a suitable alternative. Drug-Tissueoid interactions, T cell migration, and validation of the tumor characteristics like necrosis, angiogenesis, EMT etc., broaden its scope in the modern discovery landscape.

10:10 am

Session Wrap-Up

Panel Moderator:
Oliver Hill, PhD, Vice President, Drug Discovery, Apogenix AG
Panelists:
Sidi Chen, PhD, Assistant Professor, Department of Genetics and Systems Biology Institute, Yale University; Member, Yale Cancer Center and the Yale Stem Cell Center
Allison Betof Warner, MD, PhD, Assistant Attending Physician, Memorial Sloan Kettering Cancer Center
Prabuddha Kundu, PhD, Co-founder and Managing Director, Premas Biotech Pvt Ltd.
10:30 am Coffee Break - View our Virtual Exhibit Hall

IMPROVING IMMUNOTHERAPY TARGET IDENTIFICATION

10:50 am

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

Marvin Gee, PhD, Co-Founder & 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.

AGONIST IMMUNOTHERAPY

11:10 am

IL-15-Based Trifunctional Antibody-Fusion Proteins with Costimulatory TNF-Superfamily Ligands for Cancer Immunotherapy

Dafne Müller, PhD, Group Leader, Institute of Cell Biology and Immunology, University of Stuttgart

In order to support the generation and efficacy of an antitumor response, we have designed trifunctional antibody-fusion proteins for tumor-directed combined delivery of IL-15 and costimulatory members of the TNF-superfamily, demonstrating enhanced immune responsiveness in vitro and antitumor activity in a mouse model in vivo.

11:30 am

HERA-GITRL: A Unique Hexavalent GITR Agonist for Cancer Immunotherapy

Oliver Hill, PhD, Vice President, Drug Discovery, Apogenix AG

HERA-GITRL is a member of a novel class of hexavalent TNFR superfamily agonists that share the natural ligand conformation. The biological activities of HERA-GITRL, boosting antigen-specific T cell response and anti-tumor efficacy in mouse models, are crosslinking independent. As the Fc-mediated mixed mode of actions observed for antibodies are avoided, HERA-GITRL is an excellent candidate for further development into a next-generation GITR agonistic immuno-oncology drug.

11:55 am

Session Wrap-Up

Panel Moderator:
Adam Adler, Professor, Department of Immunology, UConn Health School of Medicine
Panelists:
Dafne Müller, PhD, Group Leader, Institute of Cell Biology and Immunology, University of Stuttgart
Oliver Hill, PhD, Vice President, Drug Discovery, Apogenix AG
Marvin Gee, PhD, Co-Founder & Head, Target Discovery, 3T Biosciences
12:15 pm Lunch Break - View our Virtual Exhibit Hall

IMPROVING CAR-T EFFICACY AND SAFETY

12:45 pm

CAR T Cells for T Cell Malignancies

Maksim 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.

1:05 pm

Cytokine Storm after COVID-19: Lessons Learned from CAR T Cell Therapy

Saad 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.

Basile Siewe, Director, Business Development-JAX Services, The Jackson Laboratory
1:50 pm

Session Wrap-Up

Panel Moderator:
Adam Adler, Professor, Department of Immunology, UConn Health School of Medicine
Panelists:
Saad Kenderian, PhD, Assistant Professor, Medicine and Oncology, Mayo Clinic College of Medicine
Maksim Mamonkin, PhD, Assistant Professor, Center for Cell and Gene Therapy, Baylor College of Medicine
Basile Siewe, Director, Business Development-JAX Services, The Jackson Laboratory
2:10 pm Refresh Break - View Our Virtual Exhibit Hall
2:30 pm Problem Solving Breakout Discussions - Part A

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges.

TABLE 4: CAR T Safety 

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
3:00 pm Refresh Break - View Our Virtual Exhibit Hall
3:20 pm Problem Solving Breakout Discussions - Part B
3:50 pm Refresh Break - View our Virtual Exhibit Hall

PLENARY KEYNOTE SESSION

4:10 pm

Chairperson's Remarks

K. Dane Wittrup, PhD, CP Dubbs Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology
4:15 pm

From Energy to Machine Learning

George M. Church, PhD, Robert Winthrop Professor, Genetics, Harvard Medical School

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 Ph.D. students (Dantas, Raman, Lajoie), 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.

4:40 pm

The Case for Intelligent Design in Protein Engineering

Jamie B. 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.

5:15 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
K. Dane Wittrup, PhD, CP Dubbs Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology
Panelists:
George M. Church, PhD, Robert Winthrop Professor, Genetics, Harvard Medical School
Jamie B. Spangler, PhD, Assistant Professor, Biomedical Engineering and Chemical & Biomolecular Engineering, Johns Hopkins University
5:35 pm Happy Hour - View our Virtual Exhibit Hall
6:10 pm Close of Day

Tuesday, September 1

ADVANCING NK-BASED THERAPIES

9:05 am KEYNOTE PRESENTATION:

Targeting NK Cells to Treat Cancer: Individual to Off-the-Shelf Products

Jeffrey 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, trispecific 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.

9:25 am

Leveraging NK Cells in IO Combinations for Treatment of Solid Tumors

Alicja J Copik, PhD, Asst Scholar & Core Mgr, Univ of Central Florida
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.

10:10 am

Session Wrap Up

Panel Moderator:
Conrad Russell Y. Cruz, PhD, Director, Translational Research Labs; Assistant Professor, Center for Emerging Technologies Immune Cell Therapy, Children's National Health System
Panelists:
Jeffrey Miller, MD, Professor of Medicine, Deputy Director, Masonic Cancer Center, Division of Hematology, Oncology and Transplantation, University of Minnesota
Alicja J Copik, PhD, Asst Scholar & Core Mgr, Univ of Central Florida
Tina Kang, Senior Scientist, Discovery, GenScript ProBio
10:30 am Coffee Break - View our Virtual Exhibit Hall

ADVANCES IN NK/GAMMA DELTA CELL-BASED THERAPY

11:10 am

Cord-Blood-Derived NK Cells

Conrad Russell Y. Cruz, PhD, Director, Translational Research Labs; Assistant Professor, Center for Emerging Technologies Immune Cell Therapy, Children's National Health System

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

Shireen Khan, PhD, Senior Director of Biologics, Biologics Discovery, ChemPartner

In this talk, we will discuss combining multiple methods, including immunization strategy, single plasma B cell cloning on the Beacon platform and the use of transgenic animals to significantly reduce the cycle times while rapidly identifying high affinity functional antibodies.

11:55 am

Session Wrap-Up

Panel Moderator:
Lawrence Lamb, Jr., PhD, Executive Vice President & CSO, Incysus Therapeutics, Inc.
Panelists:
Conrad Russell Y. Cruz, PhD, Director, Translational Research Labs; Assistant Professor, Center for Emerging Technologies Immune Cell Therapy, Children's National Health System
Shireen Khan, PhD, Senior Director of Biologics, Biologics Discovery, ChemPartner
Linda Masat, V.P. Business Development, Business Development, Trianni Inc.
12:15 pm Lunch Break - View Our Virtual Exhibit Hall

ADVANCING GAMMA DELTA-BASED THERAPIES

12:50 pm

BTN3A and BTN2A are New Immune-Checkpoint-Targeting Vg9Vd2 T Cell Functions against Cancer Cells

Daniel Olive, MD, PhD, Head, Tumor Immunology, Marseille Cancer Research Center

Vγ9Vδ2 T cell activation leads to broad functional activities against tumors. Tumor-infiltrating γδ T cells are 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.

1:10 pm

Development of a Next-Generation Anti-Cancer Immunotherapy: A Humanized anti-BTN3A Antibody that Activates Gamma-Delta (Vg9-Vd2) T Cells

Alem Truneh, PhD, Co-Founder & CTO, ImCheck Therapeutics SAS

ImCheck Therapeutics is developing a first-in-class activating, humanized antibody to butyrophilin 3A (BTN3A) for the treatment of cancer. ICT01 binds to BTN3A, and specifically primes a broad range of tumor cells for killing by gamma-delta (Vg9-Vd2) T cells. ICT01 has entered early-stage clinical trials in solid tumors and hematological malignancies. Therapeutic antibodies targeting several novel butyrophilins are also currently at various stages of preclinical development. This opens a new space, clearly differentiated from the current B7/CD28 family of targets, potentially ushering in an unexplored novel avenue for next-generation cancer immunotherapy.

Benjamin Doranz, PhD, MBA, President and 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.

1:55 pm

LIVE Q&A: Session Wrap-up

Panel Moderator:
Alem Truneh, PhD, Co-Founder & CTO, ImCheck Therapeutics SAS
Panelists:
Daniel Olive, MD, PhD, Head, Tumor Immunology, Marseille Cancer Research Center
Benjamin Doranz, PhD, MBA, President and CEO, Integral Molecular
2:15 pm Refresh Break - View our Virtual Exhibit Hall

NOVEL APPLICATIONS OF CELL-BASED THERAPIES

2:35 pm

Engineering Novel Targeted Cell Therapies for the Treatment of Immune Disorders

Anthony Conway, PhD, Associate Director, Cell Therapy, Sangamo Therapeutics

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 preclinical data for several technology platforms and therapeutic programs.

2:55 pm

Engineering Cell Therapy against Alloimmunity

Feiyan Mo, Graduate Student, 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.

3:15 pm

LIVE Q&A: Session Wrap-up

Panel Moderator:
Alem Truneh, PhD, Co-Founder & CTO, ImCheck Therapeutics SAS
Panelists:
Anthony Conway, PhD, Associate Director, Cell Therapy, Sangamo Therapeutics
Maksim Mamonkin, PhD, Assistant Professor, Center for Cell and Gene Therapy, Baylor College of Medicine
Feiyan Mo, Graduate Student, Baylor College of Medicine
3:35 pm Close of Improving Immunotherapy Efficacy and Safety





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