BiME®, a Unique Platform to Unlock the Power of Macrophages
Macrophages are important cells of our innate immune system and play a vital role as an orchestrator in the tumor microenvironment (TME).
Macrophages are generally categorized into two main types: M1 and M2 macrophages. The M1 phenotype plays a critical role in the immune responses to outside substances, and thus having anti-tumor effects in TME, whereas the M2 phenotype has an anti-inflammatory role that promotes tissue repair, thereby helping tumor grow.
Macrophages that participate in the formation of TME, which are also termed as Tumor-associated macrophages (TAMs), sometimes constitute up to 50% of the tumor mass and significantly contribute to the suppressive nature of the TME.
Reversing M2 macrophage into M1 phenotype and activating its phagocytosis of tumor cells have been proven an effective approach and expected as the next frontier in cancer immunotherapy.
What is BiME®?
Macrophage phagocytic activity is controlled by both “eat-me” and “don’t-eat-me” signals. Tumor cells often express high levels of CD47, a protein that transmits a “don’t-eat-me” signal which is received and deciphered by SIRPα, a protein expressed on the surface of macrophages. The “don’t-eat-me” signal interaction between CD47 and SIRPα allows tumor cells to evade the phagocytosis by macrophages.
BiME® is a proprietary bispecific antibody-based platform that simultaneously binds to the inhibitory receptor of SIRPα on macrophages and a specific antigen on tumor cells, known as tumor associated antigen (TAA), such as PD-L1 and CLDN18.2.
On one hand, the SIRPα antibody blocks the “don’t-eat-me” signal. On the other hand, the TAA antibody provides an “eat-me” signal through activation of Fc receptor on the surface of macrophages. Ultimately, this leads to the strong activation of phagocytosis and directly killing of tumor cells. Besides phagocytosis killing of tumor cells, BiME could also reprogram tumor associated macrophages to M1-like phenotype.
Why is BiME® a Disruptive Technology?
From application perspective, macrophages are abundant in essentially most types of solid tumors, making it an ideal target for both blood and solid cancers, especially cold tumors with high TAM infiltration. More important, BiME® is less likely to cause cytokine storm, a challenge confronting other T cell engaging antibodies.
Compared with CD47 targeting agents, targeting SIRPα can avoid anemia and antigen sinking side effects. One important aspects is that our uniquely optimized BiME®-SIRPα antibody is a pan-acting SIRPα that targets major SIRPα variants, covering a larger patient population with significant unmet needs.
Compared with other macrophage-based combo therapy, the bispecific modality design of BiME® molecules has greater potential in achieving single agent efficacy while reducing off-target side effects.
BiME® Molecules
BiME® molecules are a type of bispecific antibody-based platform designed to target cancer cells by activating both M1 and M2 macrophages. They are engineered with an optimized SIRPα-targeting domain that binds to macrophages, while the tumor-targeting arms designed to target specific tumor associated antigens (TAA)s.
By blocking the “don’t-eat-me” signal and providing an “eat me” signal through Fc receptor engagement, BiME® molecules lead to strong activation of phagocytosis and reprogramming of tumor associated myeloid cells. This unique design has the potential to achieve single-agent efficacy while reducing off-target side effects, making BiME® a promising new approach in cancer immunotherapy.
Learn more about BiME® molecules:
