Enhancing antibodies by engineering multi-specificity has emerged as a promising new wave in antibody therapeutics. Antibodies are empowered through binding to at least two molecular targets simultaneously, thereby delivering a highly potent therapeutic, particularly for cancer immunotherapy. This meeting will explore the challenges of engineering multi-specificity to ensure stability and efficacy, and will review the numerous forms of multi-specific antibodies in development.

Join with colleagues from around the world in this discussion of the exciting breakthroughs in engineering antibodies, and see how cancer and other applications are advancing into a true therapeutic revolution.

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THURSDAY, JANUARY 12

1:00 pm Conference Registration

1:45 Chairperson's Remarks

Matthew Robinson, Ph.D., Assistant Professor, Medical Oncology, Fox Chase Cancer Center

1:50  Bispecific Antibody Therapeutics Made by Dock-and-Lock

David M. Goldenberg, M.D., President, Garden State Cancer Center; CSO & CMO, Immunomedics, Inc. - Biography

Our group has developed a new platform technology, the Dock-and-Lock (DNL) method, which has the potential for making an unlimited number of bioactive molecules with multivalency, multifunctionality, and defined composition, generating diverse bioactive molecules of increased complexity. DNL involves the application of conjugation chemistry and genetic engineering to harness the dimerization and docking domain (DDD) of cAMP-dependent protein kinase and the anchoring domain (AD) of A-kinase anchoring proteins into respective modules capable of self-assembly and forming stably-tethered structures of defined composition. Modules may be made synthetically or genetically from proteins as well as non-proteins. Notable advantages of DNL over existing technologies include ease of manufacture with quantitative yields, and in vivo stability.

2:20  Trifunctional Antibodies: Combining Passive and Active Immunization for Cancer Therapy

Horst Lindhofer, Ph.D., Founder & CEO, TRION Pharma GmbH - Biography

Trifunctional antibodies (Triomab) have the capacity to induce long-lasting immunity.  They combine passive immunization (i.e. direct tumor cell killing) with active immunization which raises a broad immune response going beyond the tumor associated antigen originally targeted by the Triomab. This talk will focus on the trifunctional antibody, catumaxomb, which is the first approved multispecific antibody worldwide. 

2:50  Transcytosis of the Blood Brain Barrier with Bispecific Antibody Therapeutics

J. Michael Elliott, Senior Research Associate, Genentech

Bispecific antibodies are a logical next step for immunoglobulin therapeutics. Their ability to engage two unique targets simultaneously and with exquisite specificity greatly enhances potential applications of existing antibodies. We present here bispecific IgG1s with two independent Fab arms that are otherwise nearly identical to monospecific antibodies. These bispecifics are able to both cross the blood brain barrier utilizing transferrin receptor mediated transcytosis, and potently reduce amyloid-β (Ab) production in murine Alzheimer models through inhibition of the enzyme β-secretase (BACE1).

3:20  Sponsored Presentation (Opportunity Available)

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

Breakthroughs with Bispecific Antibodies

4:30  TRIBODY: Building Trispecificity by Fab-scFv Fusions

Nico Mertens, Ph.D., Director, Antibody Engineering, Biotecnol SA - Biography

Tribodies are antibody derived reagents based on fusions of different binders or effectors to the Fab chains. Due to the specific and stable heterodimerization of the Fab chains easy engineering of multispecific or multifunctional proteins is achieved. We will discuss functionality of this type of molecule as well as developability of these recombinant fusion molecules.

5:00  Bispecific Digoxigenin-Binding Antibodies for Targeted Payload Delivery

Ulrich Brinkmann, Ph.D., Scientific Director, Biologics Engineering, Roche Pharma Research and Early Development - Biography

Bispecific antibodies that bind cell-surface targets as well as digoxigenin (Dig) were generated for targeted payload delivery. Targeting moieties are IgGs that bind the tumor antigens Her2, IGF1R, CD22, or LeY. A Dig-binding single-chain Fv was attached in disulfide-stabilized form to C termini of CH3 domains of targeting antibodies. Bispecific molecules were expressed in mammalian cells and purified in the same manner as unmodified IgGs. They are stable without aggregation propensity and retain binding specificity/affinity to cell-surface antigens and Dig. Digoxigeninylated payloads were generated that retain full functionality and can be complexed to bispecific antibodies in a defined 21 ratio. Payloads include small compounds (Dig-Cy5, Dig-Doxorubicin) and proteins (Dig-GFP). Complexed payloads are targeted by the bispecifics to cancer cells and because these complexes are stable in serum, they can be applied for targeted delivery. Because Dig bispecifics also effectively capture digoxigeninylated compounds under physiological conditions, separate administration of uncharged Dig bispecifics followed by application of Dig payload is sufficient to achieve antibody-mediated targeting in vitro and in vivo.

5:30  Systems Biology Approach to the Design of Bispecific Antibody Targeting Two Redundant Pro-Survival Signaling Pathways in Cancer

Rachel Rennard, Scientist, Protein Engineering, Merrimack Pharmaceuticals

Multispecific antibody-like molecules targeting growth factor receptor signaling pathways comprise a promising new class of anti-cancer agents.  However, these multi-specific antibodies are complex, and present significant design and CMC challenges.  We have developed an integrated approach where we use mechanistic models of relevant biological systems to identify optimal molecular properties such as format, avidities and affinities.  Rational engineering approaches are then used to construct molecules with robust pharmaceutical properties.  Application of this approach to a bispecific molecule targeting two receptor tyrosine kinases will be presented.

6:00  Close of Day

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Links to Companion Meetings

Antibodies for the 21st Century

Recombinant Protein Therapeutics