Accelerated Discovery Nanobody Platform

Introduction

Since the approval of the first monoclonal antibody (mAb) 30 years ago, therapeutic mAbs and Ab-derived molecules have come to dominate the biologics market. Currently, over 100 Abs are in clinical use for different diseases, out of which more than 30 mAb target cancer.

Challenges in Therapeutic Antibody Discovery

Despite the huge market potential, multiple and complex steps make the therapeutic Ab discovery process long, expensive, laborious, and inefficient. These steps include:

1. Target identification
2. Animal immunization
3. Ab selection and engineering
4. Humanization
5. Preclinical validation

All these steps are not integrated, costly, require large equipment and facilities, and are highly dependent on experimental animals (mostly mammals, including genetically modified mice), both for immunization and for preclinical validation of the therapeutic Ab candidates.

ALADDIN Project Overview

The ALADDIN project emerges to bring to the market a novel AcceLerAteD DIscovery Nanobody platform that will increase the efficiency of therapeutic Ab discovery and preclinical validation for human cancer by:

1. Integrating selection and in vivo affinity maturation of Abs in bacterial cells holding a universal library of single domain Abs (nanobodies, Nbs) that fully eliminates animal immunization.
2. Using in silico Artificial Intelligence (AI) tools for structure-based epitope mapping, AI-guided affinity maturation, and Nb humanization.
3. Developing cost-effective miniaturized microfluidic-based devices for in vitro Ab selection from bacterial cultures.
4. Accelerating Ab validation with a fast non-mammalian in vivo model for preclinical testing based on patient-derived tumor xenografts in zebrafish larvae.
5. Impacting target and Ab validation with dynamic mathematical models to extract clinical and efficacy data of the Ab candidates.

Conclusion

These ambitious goals will be possible through the multidisciplinary ALADDIN consortium, formed by eight partners with complementary skills.