CD47 is a protein expressed on the surface of all human cells. It acts as a “don’t eat me” signal to macrophages and other phagocytic cells in the body. Cancer cells often overexpress CD47 to evade detection and phagocytosis by the immune system. antibody-drug work by blocking this “don’t eat me” signal from CD47, allowing macrophages to recognize and destroy cancer cells. When the CD47 signal is disrupted by anti-CD47 antibodies, macrophages are able to phagocytose and eliminate cancer cells through a process called phagocytosis. This restores the immune system’s ability to clear tumors and harness the body’s natural defenses against cancer.
Clinical Development Of Anti-CD47 Drugs
The first anti-CD47 drug to enter clinical trials was Magrolimab, developed by Five Prime Therapeutics. In early clinical studies, Magrolimab has shown manageable safety and hints of efficacy as a monotherapy or in combination with other anti-cancer drugs for various hematologic and solid tumors. Based on these promising initial results, Five Prime is conducting several Phase 1 and Phase 2 trials combining Magrolimab with chemotherapy or other immunotherapies to treat cancer types like acute myeloid leukemia (AML), bladder cancer and ovarian cancer.
Another Anti-CD47 Drugs that has made significant progress is Hu5F9-G4, developed by Trillium Therapeutics. In 2021, Hu5F9-G4 received Breakthrough Therapy Designation from the FDA for diffuse large B-cell lymphoma based on compelling Phase 1b data showing it can induce durable responses both as a monotherapy and in combination with rituximab. Trillium is now testing Hu5F9-G4 in several Phase 2 clinical trials for both blood cancers and solid tumors. Initial clinical data suggest it has similar safety to Magrolimab and meaningful preliminary efficacy across different cancer types.
Besides Magrolimab and Hu5F9-G4, other antibody-drug in various stages of clinical testing include TTI-622 from Tensha Therapeutics, SRF231 from Surface Oncology and ALX148 from ALX Oncology. The emerging clinical data from these early-phase trials have consistently demonstrated that blocking CD47 can restore the immune system’s ability to eliminate tumors with a tolerable side effect profile. This validates CD47 as an important immune checkpoint target for cancer therapy.
Combination Strategies With Antibody-Drug
As single agents, antibody-drug may have limited efficacy in solid tumors due to various immune escape mechanisms employed by cancers to evade phagocytosis. Therefore, combination strategies are being increasingly investigated to enhance the effect of anti-CD47 therapy. Some of the combination approaches currently under clinical evaluation include:
– Combining with chemotherapy – Chemotherapy can induce immunogenic cell death and increase exposure of eat-me signals on tumor cells, making them better targets for anti-CD47 therapy.
– Combining with other immune checkpoint inhibitors – For example, combining antibody-drug with PD-1/PD-L1 inhibitors lifts additional brakes on T cell function within the tumor microenvironment.
– Combining with cancer vaccines or cellular therapies – This stimulates both innate and adaptive immunity against tumors via synergistic mechanisms.
– Combining with tumor-targeting antibodies – antibody-drug act cooperatively with antibodies against tumor-associated antigens to elicit stronger phagocytic signaling.
Preliminary data from ongoing clinical trials suggest that anti-CD47 antibodies can improve outcomes when given with established standard-of-care agents. Further research is actively exploring new combination regimens to maximize the potential of this novel class of cancer immunotherapy.
Over the past 5 years, anti-CD47 antibodies have progressed rapidly in clinical development. Early safety and efficacy signals have validated CD47 as a promising immunotherapy target for both hematologic malignancies and solid tumors. Ongoing combination trials are helping to define the optimal ways to incorporate antibody-drug into treatment regimens across different cancer types. IF positive data continues to emerge from Phase 2 studies, some anti-CD47 antibodies may reach late-stage pivotal trials or even regulatory approval within the next 2-3 years. With further research, CD47 blockade holds great promise to extend survival and improve outcomes for many cancer patients. It has potential to become a new cornerstone of immune-based therapies against cancer.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
About Author – Ravina Pandya
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