DSP107: Advancing Cancer Immunotherapy with a Novel SIRPα-4-1BBL Dual Signaling Protein

DSP107 represents a novel fusion protein in cancer immunotherapy, engineered to stimulate both the innate and adaptive immune responses. It is designed to block the CD47/SIRPα interaction, which is a common mechanism that cancer cells exploit to evade phagocytic clearance, and to activate 4-1BB, a costimulatory receptor that enhances T-cell responses. The protein is a homotrimer, with each monomer consisting of the extracellular domains of SIRPα and 41BBL, which are essential for their respective functions.

DSP107 has been produced using a mammalian expression system and has demonstrated high binding affinity for both human CD47 and 4-1BB. It effectively blocked the SIRPα-CD47 interaction and induced phagocytosis of various cancer cell lines by immune cells. The treatment also enhanced the phagocytosis of lymphoma or carcinoma cells when used in conjunction with therapeutic antibodies such as rituximab or cetuximab.

In terms of T-cell activation, DSP107 showed the ability to activate 4-1BB signaling in the presence of CD47-expressing cells and to augment T-cell activation and proliferation. It increased the secretion of IFNγ and the expression of CD25 on T-cells, indicating its potential to bolster anti-tumor immune responses.

DSP107 is currently undergoing IND-enabling studies and CMC development, showcasing the potential of the DSP platform for targeted cancer therapies. The platform's dual targeting approach offers the possibility of a synergistic effect, combining multiple functionalities that act simultaneously.

This abstract highlights the development and functional validation of DSP107, illustrating its potential as a novel therapeutic strategy in cancer immunotherapy by harnessing both arms of the immune system to combat cancer.