Cancer is the most
acute disease and the leading cause of patient death worldwide. Both
chemotherapy and molecular-based
therapies play an important role in curing
cancer. However, the median and overall survival of patients is poor. To date, immune
therapies have changed the treatment methods for
cancer patients.
Programmed death ligand 1 (PD-L1, also known as B-H1, CD274) is a well-studied
tumor antigen. PD-L1 is overexpressed in
colon cancer,
lung cancer, and so on and plays a vital role in
cancer development. In this study, anti-PD-L1
single-domain antibodies were identified from recombinant human PD-L1 (rhPD-L1)-immunized llamas. Then, we generated a novel multifunctional anti-PD-L1-CD16a-IL15 antibody targeting PD-L1-positive
tumor cells. Anti-PD-L1-CD16a-IL15 was constructed by linking the
Interleukin-2 (IL-2)
signal peptide, anti-PD-L1
single domain antibody (anti-PD-L1-VHH) and anti-cluster of differentiation 16a
single domain antibody (anti-CD16a-VHH), and
Interleukin-15/
Interleukin-15 receptor alpha (
IL15/IL-15Rα). This anti-PD-L1-CD16a-IL15 fusion
protein can be expressed and purified from HEK-293F cells. In vitro, our data showed that the anti-PD-L1-CD16a-IL15 fusion
protein can recruit T cells and drive natural killer cells (NK) with specific killing of PD-L1-overexpressing
tumor cells. Furthermore, in the xenograft model, the anti-PD-L1-CD16a-IL15 fusion
protein inhibited
tumor growth with human peripheral blood mononuclear cells (PBMCs). These data suggested that the anti-PD-L1-CD16a-IL15 fusion
protein has a latent function in antitumour activity, with better guidance for future
cancer immunotherapy.