Cambridge Healthtech Institute’s Inaugural Symposium

Bioassays for Immuno-Oncology

Biological Assay Selection, Development, and Standards to Ensure FDA Approval of Novel Immunotherapies

October 23, 2017 | The Westin Alexandria | Washington, DC

 

Biological assays demonstrating drug characteristics such as potency, mechanism-of-action, and stability, are one of the most critical components of an FDA biologic submission. However, with more complex mechanisms-of-action, immunotherapies add a layer of difficulty to bioassay selection and development. At Cambridge Healthtech Institute's Inaugural Bioassays for Immuno-Oncology symposium, experts in bioassays for immuno-oncology therapies will discuss selection, development, and standards for bioassays and immunoassays. Special attention will be given to understanding the mechanism-of-action for immunotherapies, whether they be antibody- or cell-based. Overall, this one-day immersive symposium will outline a product life cycle approach for developing and implementing biological assays from preclinical studies to clinical development.

Final Agenda

MONDAY, October 23

9:00 am Registration & Morning Coffee

PRECLINICAL BIOASSAYS

9:25 Chairperson's Opening Remarks

Sofie Pattijn, CTO, ImmunXperts

Sofie_Pattijn9:30 KEYNOTE: In vitro Bioassays to Accelerate Immuno-Oncology Drug Development

Sofie Pattijn, CTO, ImmunXperts

Early evaluation of the effectiveness of candidate therapeutics and combination therapies can be done using mouse models and in vitro bioassays with mouse or human immune cells. The use of customized in vitro assays supports the candidate selection and functionality testing of new oncology leads.

10:00 Measurement of Fc Effector Function Using Binding Assays for Product Characterization

LeeAnn_MachieskyLeeAnn Machiesky, Scientist, MedImmune

Measuring Fc effector functions is important for antibody product characterization. As an alternative to cell-based assays, surface plasmon resonance (SPR)-based assays are useful and sensitive methods for assessing the binding affinity of the Fc to a panel of Fcγ receptors including FcRn. The talk will discuss the application of SPR assays for measuring Fc binding of different antibody subtypes, varying glycosylation levels and those with point mutations.

10:30 Networking Coffee Break

11:00 Modeling Macrophage T Cell Interactions in vitro to Support I/O Drug Discovery

Jennifer_KoenitzerJennifer Koenitzer, Ph.D., Research Investigator, Discovery Biology, Immuno-Oncology Drug Discovery, Bristol-Myers Squibb

Macrophages, highly plastic immune cells of innate myeloid origin, are frequently found as a major component of the leukocytic infiltrate in the tumor microenvironment. A growing body of evidence supports both tumor-promoting as well as tumoricidal roles for those macrophages, depending on their polarization status. The immune suppressive function of tumor-associated macrophages (TAM), in particular their ability to suppress the activity and proliferation of cytotoxic T cells, is of great interest in immuno-oncology (I/O) research and provides a rich area for discovering new drug targets that can synergize with PD-1 checkpoint blockade. Sourcing primary tumor samples and isolating sufficient numbers of TAMs for larger scale functional studies and drug candidate screening is challenging, necessitating the use of alternative methods. Herein we describe the development of an in vitro suppression assay that utilizes healthy human donor PBMC derived CD14+ monocytes, their maturation and polarization into pro- (M1) and anti-inflammatory (M2) macrophages and co-incubation with Cell Trace Violet labeled human CD8+ T cells to monitor the latter’s proliferative ability. We show that M2 macrophages robustly inhibit the proliferation of T cells compared to M1. We also present evidence on the plasticity of common M1/M2/TAM markers, such as CD206, CD163, HLA-DR & CD40; that depend on both the donor and the polarization conditions. Finally, we investigate the mechanistic aspects of suppression in vitro and provide evidence that this assay setup is a very useful tool to illuminate the mechanism of action of therapeutic antibody candidates in an I/O context.

UNDERSTANDING MECHANISM-OF-ACTION

11:30 Bioassays for Checkpoint Inhibitors

Ulrike_HerbrandUlrike Herbrand, Ph.D., Scientific Supervisor, Research & Development, Biosafety & Bioassay Services, Charles River Labs

Immune checkpoint therapy, which targets regulatory pathways in T cells to amplify antitumor immune responses, has been a game-changer in the treatment of some cancers. Bioassays to monitor immune responses are extremely challenging if the assay is designed based on primary cells to mimic the in vivo mechanism of action (MoA) in an in vitro approach. Surrogate assays reflect the MoA in a much less variable format, thereby allowing these assays to be used in GMP bioactivity testing. Surrogate assays are stability-indicating and suitable for biosimilarity assessment.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:00 Session Break

CLINICAL STAGE ASSAYS

1:55 Chairperson's Remarks

Steven J. Kussick, M.D., Ph.D., Associate Medical Director, Director, Contract Research and Flow Cytometry, PhenoPath Laboratories; Clinical Assistant Professor, Laboratory Medicine, University of Washington

2:00 Flow Cytometric Assessment of Therapeutic Targets and Immune Responses in Immuno-Oncology

Steven_KussickSteven J. Kussick, M.D., Ph.D., Associate Medical Director, Director, Contract Research and Flow Cytometry, PhenoPath Laboratories; Clinical Assistant Professor, Laboratory Medicine, University of Washington

This presentation will have two major components: 1) description of 10-color flow cytometry-based strategies for identifying and quantifying potential therapeutic targets on hematopoietic cancers including lymphoma, leukemia, and myeloma, with a review of receptor occupancy assessment in the presence of specific targeted therapies, and 2) description of 10-color flow cytometry-based approaches to comprehensive immune cell phenotyping, to assess global patient responses to immune checkpoint inhibitors and other immunomodulatory agents.

2:30 Host Cell Protein Immunoassays: The Case of Excess Antigen and Non-Linearity of Dilution

Matthew_RobertsMatthew Roberts, Ph.D., Investigator, Biopharmaceutical and Analytical Sciences, GlaxoSmithKline

Proper immunoassay design is essential to the reliable measurement of host cell protein (HCP) content throughout the manufacturing process used to produce biopharmaceuticals from cells. Validated platform methods offer distinct advantages toward development of product-specific residual HCP assays, however excess HCP antigen can pose issues to the design space of such methods, particularly in the form of non-linearity of dilution. Strategies on how to overcome this effect will be highlighted.

3:00 PD Analysis of MET Signaling in Fixed Tissue Specimens by Quantitative Multiplex Immunofluorescence and Concordance with Extraction Assays

Tony_NavasTony Navas, Ph.D., Senior Scientist, Clinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research

Development of immunofluorescence assays for phosphorylated TK biomarkers in tumor biopsies is hindered by factors including stability of phospho-epitope and specificity/sensitivity of signal detection. This talk will discuss development of phospho- and total MET IFA in FFPE tissues and its correlation with ELISA assays in extracted tissue samples. This talk will also discuss the specific quantitation of MET biomarkers localized either in the plasma membrane or nucleus in tissue sections.

3:30 Networking Refreshment Break

Promega BLACK4:00 Building a Reporter Gene Bioassay Platform for Single and Combination Immunotherapy Programs

Jey_ChengJey Cheng, Ph.D., R&D Group Leader, Bioassay Development, Promega


 

 4:30 Closing Panel Discussion: Challenges in Bioassay Design for Immuno-Oncology

Moderator:
Steven_KussickSteven J. Kussick, M.D., Ph.D., Associate Medical Director, Director, Contract Research and Flow Cytometry, PhenoPath Laboratories; Clinical Assistant Professor, Laboratory Medicine, University of Washington

  • Bioassays for determining immune response
  • Assay design
  • Drug development assays
  • Flow-cytometry cased assays

Panelists:
Ulrike_HerbrandUlrike Herbrand, Ph.D., Scientific Supervisor, Research & Development, Biosafety & Bioassay Services, Charles River Labs


Tony_NavasTony Navas, Ph.D., Senior Scientist, Clinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research


Jennifer_KoenitzerJennifer Koenitzer, Ph.D., Research Investigator, Discovery Biology, Immuno-Oncology Drug Discovery, Bristol-Myers Squibb


5:00 Close of Symposium

OutlookYouTubeFacebookLinkedInTwitter
#IMN17

Japan-FlagKorea-FlagChina-Simplified-FlagChina-Traditional-Flag  

Register Now

Download 2017 Brochure

Sponsorship and Exhibit

Conference at a glance

Celebrating 25 years