In-vivo model visualization using synchrotron techniques

Purpose and goal

Protein and peptide-based therapies face several challenges that make it difficult to optimize e.g., sequence and overall properties of the construct e.g., in an in-vivo environment. This project aims to demonstrate the potential of early-stage synchrotron light-based techniques in therapeutic drug development. Strike Pharma AB has developed a new antibody format, called Adaptable Drug Affinity Conjugate (ADAC), to more effectively activate T cells. The goal is to develop a method that investigates structural protein changes when antigen peptides bind to the antibody.

Expected effects and result

By using synchrotron light-based techniques in the early evaluation of therapeutic candidates, we can avoid falsely rejecting candidates due to problems such as oligomerization or aggregation, which are usually not detected with other analytical tools. We can thus establish a potential standard for screening in an in-vivo-like environment before the in-vivo evaluation. Finally, by combining insights from SAXS with existing knowledge, we can improve the design of synthetic peptides and make ADAC an efficient and personalized drug platform.

Planned approach and implementation

In order to study structural changes in antibody-peptide interactions under different in-vivo-like conditions, X-ray diffraction (SAXS) at MAX IV will be evaluated. SAXS is integrated with asymmetric flow fractionation (AF4) to improve understanding of structural dynamics and optimize ADAC design. AF4-SAXS-metoden enables component separation without the need for a stationary phase, which provides insights into in-vivo-like conditions in serum for the ADAC construct. The project consortium consists of Strike Pharma AB, Lunds Tekniska Högskola and RISE.