Senior Scientist II Proteintech, Illinois, United States
Disclosure(s):
Annika Dalheim, MS: No financial relationships to disclose
Introduction/Rationale: Immuno-oncology is a rapidly growing field with an urgent need for well-characterized and highly specific research reagents, particularly in immune checkpoint targeting and acute myeloid leukemia (AML). We have developed recombinant monoclonal nanobodies (VHHs) targeting these critical areas to facilitate research with minimal artifacts and to support the development of new drug candidates. This work addresses current challenges in the field by providing tools that enhance the specificity and reliability of research outcomes.
Methods: Based on our extensive experience in the field of nanobodies, we have developed VHHs that bind to key immune checkpoint proteins, including TIGIT, TIM3, LAG3, PD1, PD-L1 and CTLA4. Additionally, we have generated VHHs specific to AML typic targets, such as MSLN and FLT3. Each candidate was characterized regarding its affinity, specificity and bound epitope across different applications, including flow cytometry, immunofluorescence or live-cell imaging.
Results: n/a
Conclusion: VHHs offer several advantages over conventional antibodies: Their unique structure allows VHHs to bind epitopes different from conventional antibodies. Their monoclonal monovalent nature prevents cross-linking of target proteins, minimizing unwanted side effects such as rapid receptor internalization or activation of intracellular signaling cascades. The absence of an Fc region provides flexibility in combining VHHs with other primary and secondary antibody reagents, while also preventing unwanted Fc signaling, even during extended experiments. Directed and precise labeling with dyes allows quantification of the bound target molecules.