Praluzatamab: Unveiling the Promise of CD47-Targeted Therapy in Cancer Research

Praluzatamab is a humanized IgG4 monoclonal antibody specifically engineered to target CD47—a ubiquitously expressed transmembrane protein that is often overexpressed on the surface of various cancer cells. CD47 interacts with signal regulatory protein alpha (SIRPα), which is found on macrophages and other myeloid cells. This interaction delivers a “don’t eat me” signal that prevents phagocytosis, allowing malignant cells to escape immune surveillance and persist in the body.

By binding to CD47, Praluzatamab blocks this immune checkpoint pathway, disrupting the CD47–SIRPα interaction. As a result, macrophages and dendritic cells can more readily identify, engulf, and eliminate cancerous cells through antibody-dependent cellular phagocytosis (ADCP). This makes Praluzatamab part of an emerging class of innate immune checkpoint inhibitors that aim to restore the immune system’s ability to clear tumors—particularly through the activation of the myeloid compartment.

Unlike earlier CD47-targeting antibodies, Praluzatamab is designed with improved selectivity and reduced affinity for red blood cells, thereby minimizing the risk of anemia and other hematologic toxicities commonly seen with CD47 blockade. It has shown promise in combination with agents such as azacitidine and rituximab, indicating potential synergistic effects when used alongside other immunomodulatory or cytotoxic therapies.

With ongoing interest in CD47 as a critical immuno-oncology target, Praluzatamab continues to attract attention for its therapeutic potential across hematologic malignancies and solid tumors. Its development reflects a broader shift toward enhancing innate immune responses and overcoming tumor-induced immune evasion, marking it as a significant player in next-generation cancer therapeutics.

Praluzatamab has been actively investigated across a spectrum of hematologic and solid malignancies, gaining particular recognition for its role in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These diseases, especially prevalent among elderly and treatment-refractory populations, present a critical unmet need where traditional therapies often fall short. Praluzatamab’s ability to engage the innate immune system makes it a promising candidate for addressing this therapeutic gap.

In early studies, Praluzatamab was evaluated in combination with azacitidine, a hypomethylating agent commonly used in MDS and AML. This combination was designed to enhance immune priming—azacitidine reactivates silenced genes and exposes tumor antigens, while Praluzatamab unblocks macrophage-mediated phagocytosis. Although some clinical trials were paused or discontinued due to design or safety issues, the mechanistic synergy between these agents remains a foundational concept for ongoing and future research into CD47-targeted therapies.

Beyond AML and MDS, Praluzatamab has been explored in B-cell non-Hodgkin lymphoma, particularly in combination with rituximab. This dual-target strategy leverages rituximab’s ability to mark malignant B cells and Praluzatamab’s checkpoint-blocking function to promote effective immune clearance. Early data suggested potential additive effects, pointing to a broader immunotherapeutic role in hematologic cancers.

In solid tumors such as ovarian, lung, and gastric cancers, Praluzatamab has been assessed for its ability to enhance innate immune responses where T-cell–based therapies often fail due to immunosuppressive microenvironments. Though early trials faced limitations, including toxicity concerns and slow enrollment, these insights have shaped more refined strategies in dosing, patient selection, and combination therapy.

Emerging studies continue to optimize the use of Praluzatamab and related agents, emphasizing reduced toxicity, enhanced immune activation, and tailored regimens—confirming the drug’s relevance in the evolving field of immuno-oncology.