Improving Immunotherapy Efficacy and Safety Banner

 

Despite the clinical benefits of immunotherapies, questions still remain around efficacy, targeting and toxicity, as well as the patients these therapies will most benefit. Combinations only add to the problem, yet these are some of the most promising therapies currently in development. Cambridge Healthtech Institute’s Improving Immunotherapy Efficacy and Safety conference will detail the latest developments in predicting and improving clinical outcome, product performance, and dosing, with dedicated sessions on biomarkers, effective preclinical models and strategies to mitigate toxicity. We will also investigate manipulating the tumor microenvironment and emerging IO targets. Overall, this event will enable researchers to continue moving forward rapidly, but safely.


Final Agenda

Sunday, April 29

Recommended Short Course(s)*

SC1: Preclinical and Clinical Assessment of Immunogenicity: Multidomain Therapeutics and New Modalities, Including Gene Therapy and CAR T

SC6: Practical Considerations for Biomarker Bioanalysis


*Separate registration required.

MONDAY, APRIL 30

7:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)

 

NEW APPROACHES TO IMMUNOTHERAPY
 Waterfront 1&2

8:30 Chairperson’s Remarks

Daniel Christ, PhD, Associate Professor, Director Centre for Targeted Therapy, Garvan Institute of Medical Research

8:40 Viral Vectors for Neoantigen Immunotherapy: Driving a Potent CD8 T Cell Response

Andrew AllenAndrew Allen, MD, PhD, President & CEO, Gritstone Oncology, Inc.




9:10 Targeting Solid Tumors and Cancer Stem Cells with Prosthetic Antigen Receptor Modified T-Cells

Carston R. WagnerCarston R. Wagner, PhD, Professor, Department of Medicinal Chemistry, University of Minnesota, and CSO, Tychon Bioscience, LLC

Over the past decade, it has become increasingly clear that harnessing a cancer patient’s T-cells to destroy tumor cells will be an important weapon in an oncologist’s therapeutic arsenal. Nevertheless, although selective tumor cell killing and significant clinical success against B-cell malignancies has been demonstrated, the same level of success against solid tumors has remained elusive. To address this unmet need, our group has envisioned the potential of chemical biology and protein engineering to non-genetically modify T-cell membranes.

9:40 Cancer Immunotherapy beyond PD-1/PD-L1

Jessie_EnglishJessie M. English, PhD, Vice President, Head of Discovery, ImmunoOncology Translational Innovation Platform (TIP), EMD Serono


10:10 Networking Coffee Break (Harbor & Mezzanine Level)

ENGINEERING STRATEGIES FOR IMPROVED IMMUNOTHERAPY
 Waterfront 1&2  

10:45 Chairperson’s Remarks

Daniel Christ, PhD, Associate Professor, Director Centre for Targeted Therapy, Garvan Institute of Medical Research

10:50 Engineering Interleukin-2 for Cancer Immunotherapy

Daniel ChristDaniel Christ, PhD, Associate Professor, Director Centre for Targeted Therapy, Garvan Institute of Medical Research

Interleukin-2 is an established therapeutic agent used for cancer immunotherapy. It is generally believed that treatment efficacy is mediated by CD8+ and NK cell activity, and considerable efforts have focused on generating IL-2 variants that expand these subsets systemically. Here we describe a second and unexpected mechanism, namely the selective depletion of CD25+ CD4+ regulatory T-cells (Tregs), as a major determinant of antitumour activity. Our results outline mechanisms of action and provide important guidance for the development of next generation cytokine therapeutics.

11:20 Stem-to-T Cell, A New Approach to Immunotherapy

Steven J. SwansonSteven J. Swanson, PhD, Senior Vice President, Research, ImmunoCellular Therapeutics, Ltd.

Our early stage Stem-to-T Cell program isolates hematopoietic stem cells from cancer patients, modifies them through genetic engineering, and after re-implantation, induces production of autologous cytotoxic T cells, which would recognize and kill tumor cells. This new approach to immunotherapy may have fewer safety issues such as cytokine release syndrome than current treatments, and could provide long term surveillance against tumor recurrence. 

Mass spectrometry is the tool-of-choice to discover and validate the in vivo presence of HLA associated peptides on the tumor cell surface. Additionally, Proteomic strategies enable the copy number estimation of surface HLA- associated peptides antigens, to help in the decision-making of selecting the most effective and efficient therapeutic approach (bispecific vs CAR T cell). Current Proteomic methods complement immune-based and in silico (bioinformatics) approaches for aberrant peptide discovery.

11:50 The Use of Nanobodies to Improve Immune-Oncology Therapeutics

Carlo BouttonCarlo Boutton, PhD, Director Technology & Information Management, Ablynx

Small Nanobodies with their modular design make a perfect starting point for generating multispecific T-cell recruitment formats. The flexibility of our Nanobody platform allows the generation of T cell recruitment compounds simultaneously targeting different epitopes on one tumor anchor (biparatopics) or simultaneously targeting multiple tumor antigens (bispecifics). The benign safety profile of our TCRα/β reactive recruiter was evaluated extensively both in vitro and in vivo in non-human primates opening the opportunity for multi-specific Nanobody-based T cell recruitment therapies

Precision for Medicine12:20 pm Developing Next-Generation Targeted Cancer Therapies Requires Next Generation Immune Monitoring Tools to Guide Success

Thomas_KleenThomas Kleen, PhD, Vice President Immune Monitoring and Specialty Lab Services, Precision for Medicine

Success and failure of any immunotherapy is depended on engaging the immune system. Epiontis ID, a next generation tool based on qPCR-Assisted Cell Counting (qPACC), requires only 75ul-300ul of whole blood (or small amounts of tissue) to monitor up to 16 different human cell types. Precise and robust monitoring allows samples to be simply frozen on-site and easily shipped without any burden on clinical sites.

12:50 Luncheon Presentation I: Identifying Critical Immunotherapy Target Receptors and Assessing Target Specificity Using Cell Microarray Technology

Alex Kelly, US Business Development Manager, Retrogenix

Human cell microarray screening enables the discovery of primary cell surface receptors and off-targets for a variety of biotherapeutic molecules, including peptides, antibodies and proteins, as well as CAR T and other cell therapies. Case studies will demonstrate the utility of the technology in identifying novel immunotherapy targets as well as in specificity screening for biotherapeutics to aid safety assessment and provide key data to support IND submissions.

1:20 Luncheon Presentation II (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:50 Session Break

2:20 Problem-Solving Breakout Discussions (Commonwealth Hall)

Neoantigens for Cancer Immunotherapy

Andrew Allen, MD, PhD, President & CEO, Gritstone Oncology, Inc.

  • Tumor antigen identification by deep learning – training then illuminating
  • Viral vectors for neoantigen immunotherapy: driving a potent CD8 T cell response
  • Advances to improve monitoring of neoantigen responses

Predicting and Mediating CAR, TCR, and TIL Toxicities

Saad J. Kenderian, Assistant Professor of Medicine and Oncology, Mayo Clinic College of Medicine

  • Recognize expected toxicities after CART cell therapy
  • Preclinical modeling of cytokine release syndrome after CART cell therapy
  • Management of toxicities after CART cell therapy
  • Strategies to develop novel approaches and prevent cytokine release syndrome after CART cell therapy

3:20 Networking Refreshment Break (Harbor & Mezzanine Level)


PLENARY KEYNOTE SESSION            Amphitheater and Harborview Ballroom

 

4:00 Chairperson’s Remarks

Peter Fung, PhD, Senior Manager Product Marketing, NanoTemper Technologies

4:10 Challenges and Opportunities in Engineering Protein Biopharmaceuticals

Dane_WittrupK. Dane Wittrup, PhD, C.P. Dubbs Professor, Chemical Engineering and Biological Engineering; Associate Director, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT)

Arthur C. Clarke’s First Law posits that “When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong.” Bearing this in mind, in this talk I will highlight areas of protein drug development that appear poised for breakthroughs in the coming decade or so.

4:55 The Next Generation of Cancer Immunotherapy: Targeting Myeloid Immune Checkpoints

Kipp_WeiskopfKipp Weiskopf, MD, PhD, Resident Physician, Internal Medicine, Brigham and Women’s Hospital

Immune cells of the myeloid lineage hold tremendous potential as effectors of cancer immunotherapy. The CD47/SIRPα axis is a key molecular pathway that governs the interaction between myeloid cells and tumors. Therapies that target the interaction are effective across multiple preclinical models of cancer and are now under investigation in clinical trials. Further studies have revealed additional regulators of myeloid cell activation that can be exploited as myeloid immune checkpoints.

Precision for Medicine5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

7:15 End of Day

TUESDAY, MAY 1

8:00 am Registration (Commonwealth Hall) and Morning Coffee  (Harbor Level)

NOVEL APPROACHES TO IMMUNOTHERAPY
 Waterfront 1&2

8:25 Chairperson’s Remarks

Saad J. Kenderian, Assistant Professor of Medicine and Oncology, Mayo Clinic College of Medicine

8:30 Replicating Retroviruses for Manipulation of the Tumor Immune Ecosystem: Preclinical and Clinical Outcomes

Douglas JollyDouglas Jolly, PhD, Executive Vice President, Research & Pharmaceutical Development, Research & Pharmaceutical Development, Tocagen Inc.

Toca 511 is a replicating retroviral vector (RRV) encoding a modified yeast cytosine deaminase; Toca FC is an extended release formulation of flucytosine, metabolized to 5-FU by cytosine deaminase. RRV are tumor selective in animals and humans after intravenous or intralesional administration. Preclinical data shows direct tumor killing by 5-FU and depletion of 5-FU sensitive-immune suppressive myeloid cells leads to breaking of immune tolerance to the tumor, generation of anti-tumor immunity and long-term tumor regression.

9:00 Pexa-Vec: A Multi-Mechanistic Immunotherapeutic Modulator of the Tumor Microenvironment

Naomi De Silva, PhD, Associate Director, Preclinical and Translational Science, Clinical, Sillajen Biotherapeutics, Inc.

Pexa-Vec (pexastimogene devacirepvec, JX-594) is an oncolytic and immunotherapeutic vaccinia virus, engineered to preferentially infect tumor cells, disrupt vasculature, and stimulate anti-tumor immune responses. Clinical studies and preclinical modeling in a transgenic model of pancreatic neuroendocrine cancer demonstrates that Pexa-Vec rapidly alters the immune microenvironment, and this can be augmented with checkpoint inhibitors to improve efficacy. Combination studies and a Phase III trial evaluating Pexa-Vec in the treatment of advanced primary liver cancer is underway.

9:30 CART Cell Therapy: Beyond CD19

Saad J. KenderianSaad J. Kenderian, Assistant Professor of Medicine and Oncology, Mayo Clinic College of Medicine



 

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

IMPROVING CAR T SAFETY AND EFFICACY
Waterfront 1&2   

10:50 T Versus T: Optimizing CAR Function and Reshaping T Cell Response

Maksim MamonkinMaksim Mamonkin, PhD, Instructor, Center for Cell and Gene Therapy, Baylor College of Medicine

Shared expression of most targetable antigens between normal and malignant T-cells complicates the development of CAR T therapies to T-cell tumors. I will review current challenges in the field and present solutions to increase therapeutic potential of CAR T cells by minimizing CAR-driven T-cell fratricide and excessive differentiation.

 

11:20 Universal Immune Receptor Based Therapy for “on Demand” Application of CAR-Like Therapies

Daniel J. Powell JrDaniel J. Powell Jr., PhD, Associate Professor of Pathology and Laboratory Medicine, University of Pennsylvania



 

11:50 Exploring Optimization Parameters for Chimeric Receptors in T Cells

Kathleen McGinnessKathleen McGinness, PhD, Senior Director, Platform Technologies, Unum Therapeutics

T cells engineered to express chimeric receptors exert powerful cytotoxicity against tumors. Understanding optimization parameters for engineered T cells with respect to efficacy and safety is important for successful application to more challenging therapeutic environments. We have explored the composition of Antibody Coupled T-cell Receptors (ACTR) and the interplay between ACTR and targeting antibodies to identify design parameters to modulate and optimize engineered T cell activity.

12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

2:00 Chairperson’s Remarks

Kathleen McGinness, PhD, Senior Director, Platform Technologies, Unum Therapeutics

2:05 A Novel T Cell Therapy Engaging the Whole T Cell Receptor

Alfonso Quintás Cardama, MD, CMO, Executive Leadership Team, TCR2 Therapeutics, Inc.

We report a novel way to engineer T cells that have to potential to overcome limitations of current T cell therapies. The initiation of a broader T cell signal cascade by the engagement of all T cell receptors subunits has the potential to overcome the hostile, immunosuppressive tumor microenvironment of solid tumors and MHC-independent antigen recognition makes TRuC-T cells less vulnerable to immune escape, such as loss of MHC.    

2:35 Enhancing Adoptive Cell Therapies through Exogenous Regulation

Steven ShamahSteven Shamah, PhD, SVP, Head of Research, Obsidian

The inability to control CAR T cells once administered presents considerable toxicity and efficacy challenges in many settings. Obsidian Therapeutics is using Destabilizing Domain (DD) technology providing pharmacological control of transgene protein levels through the dosing of safe, FDA-approved drugs. We will describe our DD discovery process and update on lead programs to develop CAR T cell products that are armed with regulated cytokines for enhanced efficacy and more favorable toxicity profiles.

3:05 Assessing the Safety of TCRs

Andrew SewellAndrew Sewell, PhD, Professor, Division of Infection and Immunity, Cardiff University School of Medicine

The αβ TCR repertoire is dwarfed by the vast array of potential foreign peptide-MHC complexes. Comprehensive immunity requires that each T-cell recognizes numerous peptides and thus be extremely cross-reactive. Natural central tolerance culls T-cells that have a high affinity for self peptide-MHC. TCR engineering bypasses this process and can result in dangerous self-reactivity. These toxicities can be predicted and engineered out without loss of specificity for the target antigen. 

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

IMPROVING IMMUNOTHERAPY EFFICACY AND SAFETY
Waterfront 1&2   

4:25 TCR-Based Cancer Immunotherapy – How to Find and Select the Right TCR Candidate

Claudia WagnerClaudia Wagner, PhD, Associate Director, TCR Discovery & Validation, Immatics

Tumor-specific T-cell receptors (TCRs) can serve as potent weapons for cellular-based therapies or bispecifics approaches. Ideal TCRs are selected through extensive efficacy testing and safety profiling, including a novel high-throughput approach using information from the large collection of healthy tissues and tumor biopsies to investigate on- and off-target specificity for selected TCR candidates.

4:55 Vectorization in an Oncolytic Vaccinia Virus of Antibodies Against Programmed Cell Death -1 (PD-1) Allows Their Intratumoral Delivery and an Improved Tumor-Growth Inhibition

Jean-Baptiste Marchand, PhD, Head, Protein Sciences, Transgene

5:10 Probing Antigen Recognition of Effector T Cells in Anti-Tumor Immune Responses

Beth Pearce, Graduate Student, Koch Institute for Integrative Cancer Research, MIT


5:25 End of Improving Immunotherapy Efficacy and Safety

5:30 Registration for Dinner Short Courses (Commonwealth Hall)

Recommended Dinner Short Course(s)*

SC9: 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.


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