Indusatumab: Advancing Anti-CD47 Cancer Research with Biosimilar Innovations

Indusatumab is an experimental antibody therapy targeting CD47, a protein that enables cancer cells to evade immune destruction.

Indusatumab blocks the CD47-SIRPα interaction, restoring macrophage activity and promoting immune-mediated tumor clearance.

Indusatumab is under investigation for treating hematologic malignancies and solid tumors, particularly in combination with other immunotherapies.

Indusatumab is a monoclonal antibody designed to enhance the immune system’s ability to recognize and eliminate cancer cells by targeting CD47, a transmembrane protein known as the “don’t eat me” signal. CD47 is overexpressed in many cancers, allowing malignant cells to evade immune destruction by preventing macrophages and other immune cells from initiating phagocytosis. By blocking CD47, Indusatumab disrupts this protective mechanism, making tumors more susceptible to immune-mediated clearance.

CD47 inhibitors have emerged as a promising class of immunotherapies, but early drug candidates faced significant challenges, particularly hematologic toxicity. Since CD47 is also expressed on healthy cells, broad inhibition can lead to unintended effects, such as anemia or thrombocytopenia. Indusatumab is designed to address these concerns through selective binding and refined dosing strategies, which help minimize off-target effects while preserving therapeutic efficacy.

Studies suggest that Indusatumab may be most effective when used in combination with other cancer therapies. For example, pairing it with immune checkpoint inhibitors, such as PD-1 or PD-L1 inhibitors, may enhance anti-tumor responses by activating both innate and adaptive immunity. Additionally, combining Indusatumab with chemotherapy or radiation therapy could increase tumor cell susceptibility to immune-mediated destruction. Given its potential across multiple tumor types, Indusatumab is currently being evaluated in clinical trials to determine its safety, efficacy, and optimal therapeutic combinations. Ongoing research aims to refine its role in cancer treatment and identify patient subgroups most likely to benefit from CD47-targeted therapy.

Indusatumab exerts its therapeutic effects by disrupting CD47-SIRPα signaling, a key pathway that cancer cells exploit to evade immune clearance. CD47, a cell surface protein, binds to signal regulatory protein alpha (SIRPα) on macrophages, sending an inhibitory signal that prevents phagocytosis. By blocking this interaction, Indusatumab restores macrophage function, allowing the immune system to recognize and eliminate tumor cells more effectively.

The key mechanisms of action of Indusatumab include:

1. Blocking CD47-SIRPα Interaction – CD47’s engagement with SIRPα normally suppresses macrophage activity. Indusatumab prevents this interaction, removing the inhibitory signal and allowing macrophages to engulf and destroy tumor cells.

2. Enhancing Macrophage-Mediated Phagocytosis – By lifting the immune suppression caused by CD47, Indusatumab promotes the natural process of tumor cell elimination through macrophage-mediated phagocytosis.

3. Stimulating Adaptive Immunity – As macrophages digest tumor cells, they present tumor antigens to T cells, stimulating an adaptive immune response. This activation enhances cytotoxic T-cell infiltration into tumors, leading to more robust and long-lasting anti-cancer effects.

Preclinical models suggest that Indusatumab may also enhance the efficacy of traditional therapies, such as chemotherapy and radiation. By disrupting CD47 signaling, tumors become more vulnerable to these treatments, which in turn can increase immune-mediated clearance. Additionally, researchers are exploring ways to optimize Indusatumab’s dosing to mitigate the anemia risks associated with CD47 inhibition while maintaining its potent anti-tumor effects. Given its dual action on both innate and adaptive immunity, Indusatumab represents a promising immunotherapeutic strategy for aggressive and treatment-resistant cancers.

Indusatumab is currently under clinical investigation for its potential to treat a range of malignancies, including both hematologic cancers and solid tumors. CD47 expression is elevated in multiple cancer types, making it an attractive target for immunotherapy.

1. Acute Myeloid Leukemia (AML): CD47 is overexpressed in AML cells, contributing to immune evasion. Indusatumab enhances macrophage-mediated clearance of leukemia cells, offering a potential therapeutic strategy for improving patient outcomes. Early studies suggest that it may be particularly effective when combined with standard AML treatments such as azacitidine or venetoclax.

2. Lymphomas: Non-Hodgkin’s lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL) also exhibit high CD47 expression. Indusatumab, in combination with rituximab or other targeted therapies, has shown promise in enhancing tumor clearance and improving response rates.

1. Non-Small Cell Lung Cancer (NSCLC): CD47 expression in NSCLC tumors suggests that Indusatumab could be an effective immunotherapy option. When combined with PD-1 or PD-L1 inhibitors, it may boost immune activation and enhance tumor regression.

2. Colorectal and Ovarian Cancers: Preclinical studies indicate that Indusatumab enhances the efficacy of chemotherapy by increasing immune-mediated tumor destruction. These findings suggest a role for Indusatumab in improving outcomes for patients with these difficult-to-treat malignancies.

Ongoing clinical trials are focused on determining the most effective dosing regimens, identifying predictive biomarkers for patient selection, and optimizing combination strategies to maximize therapeutic benefit. As research progresses, Indusatumab holds significant potential to improve treatment responses and expand the scope of immunotherapy in oncology.

A biosimilar is a highly similar alternative to an original biologic therapy, developed to support research and drug discovery without being identical to the original.