51st Annual Meeting & ToxExpo - Society of Toxicology

San Francisco, California
The Thematic Track information can be found on pages 8–9.
exceptional target specificity. Initial antibody-based therapies were
designed to target a single epitope. More recently, however, multitargeting
antibodies, including nanobodies, are being designed to bind
and modulate multiple cellular targets having coordinated biological
pathways. These novel and highly specific constructs present new
challenges for assessing safety in the nonclinical setting, including
identification of pharmacologically relevant species, creative study
designs that support clinical development in the presence of speciesdependent
pharmacokinetic behavior, and antidrug antibody assay
implementation strategies for multi-anti-idiotype immunological
responses that may interfere with pharmacological/toxicological
data interpretation. This important topic will generate interest in
this issue and bring about the discussion and challenges with regard
to assessing the safety of these cutting-edge biotherapeutic modalities.
Our panel of experts will begin by providing a brief overview of
protein engineering technologies used in the design of dual-targeting
biotherapeutics with the aim of providing a basic understanding of
the technologies and particularly the toxicology-relevant aspects
of construct design, such as the influence of amino acid sequence
homology and glycosylation patterns on species-relevant pharmacologic
action. We will follow the introduction with a series of three
case studies that illustrate the unique issues faced when developing
clinical trial-enabling strategies, study design, and data interpretation.
Finally, a brief commentary from the regulatory perspective on
the need for nonclinical safety and regulatory scientists to partner
when faced with these new challenges will close out the session. At the
conclusion of the session a summary of the challenges and proactive
commentary on the future directions of nonclinical safety assessment
of dual-targeting biotherapeutics will be presented.
• Dual Target Construct Engineering for Target Specificity and
Efficacy. Jennifer Cochran, Stanford University, Palo Alto, CA.
• Nonclinical Assessment of Bispecific T Cell-Engaging
Antibodies. Benno Rattel, Micromet AG, Munich, Germany.
• Computational, Safety, and Regulatory Strategies Used
in Developing a Novel Bispecific Molecule in Oncology.
Kenneth Olivier, Merrimack Pharmaceuticals, Inc., Cambridge, MA.
• Nonclinical Characterization of a HER3 and EGFR Dual Action
Antibody in Cynomolgus Monkeys. Rodney Prell, Genentech,
South San Francisco, CA.
• Regulatory Perspective on Dual-Targeting Biotherapeutics:
Approaches, Translation of Nonclinical Findings, Challenge.
Anne Pilaro, US FDA, Washington, DC.
• Challenges and Future Directions of Multitargeting
Biotherapeutic Approaches. Warren Ku, Boehringer Ingelheim
Pharmaceuticals, Inc., Ridgefield, CT.
Symposia
The Allergenicity and Immunomodulatory
Effect of Food Substances
Wednesday, March 14, 9:00 AM to 11:45 AM
Chairperson(s): Greg Ladics, DuPont Agricultrual Biotechnology,
Wilmington, DE, and Reiko Teshima, National Institute of Health
Sciences Japan, Tokyo, Japan.
Sponsor:
Immunotoxicology Specialty Section
Endorsed by:
Food Safety Specialty Section
A food allergy is a reaction of the immune system to an otherwise
harmless protein in food. Typically, such food allergic reactions are
mediated by IgE and occur in atopic individuals who are genetically
predisposed to allergy and who have been previously sensitized to the
allergen. The incidence of food allergy ranges from approximately
1%–2% in adults and 6%–8% in children. The normal immune
response to dietary proteins is associated with the induction of oral
tolerance, a state of active inhibition of immune responses to an
antigen by means of prior exposure to that antigen via the oral route.
The mechanism(s) responsible for the development of oral tolerance
are still the subject of research and debate. This symposium will
present several hypotheses regarding the role that dietary triglycerides
and synbiotics may play in the development of oral tolerance as well
as the role immunomodulating factors (e.g., environmental factors)
may play in breaking oral tolerance to protein allergens. Additionally,
the structural and functional biology of allergenic food proteins will
be discussed along with in vitro models to predict the potential crossreactivity
of food proteins.
• Structural and Functional Biology of Allergenic Food Proteins.
Heimo Breiteneder, Medical University of Vienna, Vienna, Austria.
• Food Allergy and the Role of Dietary Triglycerides in
Sensitization and Anaphylaxis against Dietary Antigens.
Erik Eckhardt, University of Kentucky, Lexington, KY.
• Antiallergic Effects of a Specific Mixture of Oligosaccharides or
Combined with a Probiotic Strain (Synbiotics). Leon Knippels,
Danone Research, Wageningen, Netherlands.
• Food Sensitization and Its Induction by Immunomodulating
Factors. Tomoko Shindo, Hatano Research Institute, Hadano
Kanagawa, Japan.
• In Vitro Provocation Study. Ryosuke Nakamura, National Institute
of Health Sciences, Tokyo, Japan.
Scientific
up-to-date information at www.toxicology.org 79
Thematic Session