LAUNCHPAD: Discovery Platform for Target-Specific Antibodies

LAUNCHPAD (the Lab for Antibody & Nanobody Phage Display & Discovery) leverages a fully human antibody library in two formats — VHH and scFv — built from custom donor diversities to generate drug-like antibody binders against targets of interest. Using this library, our team supports phage and yeast display-mediated antibody discovery and screening workflows, tailoring services to the needs of each individual program.

Custom, Fully Human Antibody Library and Scalable Workflows

Our custom, fully human library is available in VHH and scFv formats with theoretical diversities of 10²⁶ for scFv formats and 10¹⁶ for VHH formats. Libraries are built using a Gen3L architecture from Specifica and packaged in phage, yielding pannable libraries of 10¹⁰ to 10¹² that can be used to identify between 10⁵ to 10⁶ target-specific antibodies through in vitro display.

Following selection, next-generation sequencing and other bioinformatics workflows can be used to downselect approximately 100 antibodies for further functional characterization. If needed, affinity maturation can be used to improve the affinity of one or two lead candidates and identify thousands of optimized sequences for further exploration through IMPACT².

Workflow and Services

Phage and/or Yeast Display
For Fine-Tuning of Affinities, Specificity, and Expression

NGS
And Bioinformatics-Driven
Clone Selection

Functional Characterization
And Soluble VHH Production

Affinity Tuning
And Binder Optimization

Antibody Discovery of Target-Specific Binders

Our antibody discovery platform comes with capabilities to perform initial rounds of phage display against either a recombinant or cell surface target. These initial rounds of phage display, to ensure enrichment of target-specific binders, can be followed yeast display against either the recombinant or cell surface target to fine-tune for specific threshold affinity or epitope targeting profiles.

Selected outputs, in either phage or yeast format, can be screened and sequenced as individual clones to identify, in collaboration with the investigator, target-specific, sequence liability-free antibodies with desired affinity and epitope targeting profiles.

Enhanced Binder Discovery via Next Generation Sequencing (NGS)

While cherry picking clones and Sanger sequencing of picked clones from selected phage and/or yeast outputs will constitute our base workflow, our team can also perform, in collaboration with a sequencing partner, Illumina-based sequencing to deep sequence select phage or yeast outputs, enabling enhanced binder discovery and the identification of additional clones that either display round-to-round enrichment or are sequence-similar to hits identified by Sanger sequencing. Investigators will be provided with access to the NGS results for each sequenced output and can work with our team to identify antibody sequences for further investigation.

Soluble Antibody Production & Characterization

Selected antibody binders will be produced as soluble antibodies using our HT, crude protein production workflow and characterized for: (1) human/cyno/mouse cross-reactivity, (2) epitope binning or competition against a known benchmark antibody, (3) affinity, and/or (4) functional activity.

Affinity Tuning & Binder Optimization

Antibodies with the appropriate binding profile can be affinity matured or otherwise optimized for enhanced properties. Through diversity-generating strategies (i.e. CDR shuffling and saturation mutagenesis), we generate libraries of variants around a lead “parental” antibody that can be mined via phage or yeast display to identify function- or affinity-improved variants.

What's Next?

Once promising hits have been identified, investigators can leverage IMPACT² to engineer them into therapeutic formats and run pooled and arrayed functional screens to identify lead candidates.

Explore IMPACT²

Interested in collaborating?

Complete our brief project interest form to share your project background, goals, target, and services of interest.

Project Interest Form

Working with LAUNCHPAD

LAUNCHPAD services are available to Dana-Farber Cancer Institute investigators and other Harvard Medical School (HMS) affiliates. Our engagements are collaborative and tailored. We partner with PIs to define screening goals, decision points, and deliverables, then customize the discovery workflow on a project-by-project basis.

If you're an HMS affiliate with expertise in disease biology and drug development and you're interested in working with us, please reach out. We'll assess feasibility and work with you to develop a workflow to meet your program’s needs.

Contact

Faculty Director: Eric L. Smith, MD, PhD
Head of Research: Anusuya Ramasubramanian, PhD

Harvard Institutes of Medicine
Room 105 (office) and Room 115 (lab)
4 Blackfan St
Boston, MA 02115