anti cd47 monoclonal antibody cc 90002

Drug Overview

The medication known as anti cd47 monoclonal antibody cc 90002 (also identified as CC-90002) is an investigational, humanized monoclonal antibody designed to treat aggressive blood cancers and solid tumors. It acts as an immune checkpoint inhibitor, specifically targeting the “Don’t Eat Me” signal that cancer cells use to hide from the immune system.

Developed originally by Celgene (now Bristol Myers Squibb), CC-90002 is a high-affinity IgG4 antibody. Its primary mission is to block the interaction between a protein called CD47 on cancer cells and the SIRP\alpha receptor on macrophages (the “clean-up” cells of the immune system). By breaking this connection, the drug “unmasks” the cancer, allowing macrophages to recognize, engulf, and destroy the malignant cells.

• Generic Name: CC-90002.
• Drug Class: Humanized IgG4 anti-CD47 Monoclonal Antibody.
• Target: CD47 (Integrin-Associated Protein / IAP).
• Route of Administration: Intravenous (IV) infusion.
• FDA Approval Status: Discontinued/Inactive. As of March 2026, CC-90002 is not FDA-approved. Clinical development was halted following Phase I trials (NCT02641002 and NCT02367196) due to a lack of sufficient clinical activity as a single agent (monotherapy) and the frequent development of anti-drug antibodies (ADAs) in patients, which neutralized the drug’s effectiveness.

What Is It and How Does It Work? (Mechanism of Action)

The “Don’t Eat Me” Signal

Healthy cells express CD47 to tell macrophages not to eat them. Many types of cancer—including AML, lymphoma, and various solid tumors—”hijack” this system by overexpressing CD47. This effectively paralyzes the macrophages, allowing the tumor to grow unchecked.

Molecular Level Mechanisms

1. Checkpoint Blockade: CC-90002 binds to CD47 on the surface of the tumor cell with high affinity.
2. SIRP\alpha Inhibition: By coating the CD47 protein, the antibody physically blocks it from binding to the SIRP\alpha receptor on macrophages.
3. Restoration of Phagocytosis: With the “Don’t Eat Me” signal blocked, the macrophage can now respond to “Eat Me” signals (like calreticulin) on the cancer cell.
4. Engulfment: The macrophage is triggered to perform phagocytosis, literally eating the cancer cell.
5. Differentiated Design: Unlike some other CD47 antibodies, CC-90002 was specifically engineered (using an IgG4 backbone) to avoid hemagglutination (clumping of red blood cells), a side effect that has plagued other drugs in this class.

FDA Approved Clinical Indications

There are currently no FDA-approved indications for CC-90002.

Before development was halted, the drug was investigated in the following settings:

• Relapsed or Refractory Acute Myeloid Leukemia (AML): For patients who had failed standard induction therapy.
• High-Risk Myelodysplastic Syndromes (MDS): Particularly for patients at high risk of transforming into full leukemia.
• Relapsed/Refractory Non-Hodgkin Lymphoma (NHL): Investigated in combination with Rituximab.
• Advanced Solid Tumors: Exploratory studies in various metastatic cancers.

Dosage and Administration Protocols

Because the drug was discontinued during Phase I, there is no “standard” dose. The following information is based on the dose-escalation protocols used in the CC-90002-AML-001 and CC-90002-ST-001 trials.

Clinical Efficacy and Research Results

The clinical results for CC-90002 provided critical insights into the limitations of targeting CD47 as a standalone therapy.

• Lack of Monotherapy Activity: In the AML and MDS trials, no objective responses (significant tumor shrinkage) were observed when CC-90002 was used alone.
• Combination Success: In the Non-Hodgkin Lymphoma trial, CC-90002 combined with Rituximab showed an Overall Response Rate (ORR) of 13%, including one durable complete response. This proved that CD47 blockade works best when “primed” by another antibody.
• Anti-Drug Antibodies (ADAs): A major hurdle was that patients’ immune systems recognized CC-90002 as foreign and created ADAs, which cleared the drug from the body prematurely, particularly after the first cycle of treatment.

Safety Profile and Side Effects

CC-90002 was designed to be safer for red blood cells than its competitors, but it still carried significant hematologic risks.

Common Side Effects (>20%):

• Neutropenia: A drop in white blood cell counts (reported in ~38% of lymphoma patients).
• Thrombocytopenia: A drop in platelet counts (21%).
• Anemia: While the drug avoided “bursting” red blood cells (hemolysis), it still caused a general drop in red cell counts in many patients.
• Infusion-Related Reactions (IRR): Chills, fever, or shortness of breath (dyspnea) during the infusion.

Serious Adverse Events:

• Cytokine Release Syndrome (CRS): Rare cases of systemic inflammation.
• Hepatotoxicity: Elevation of liver enzymes (AST/ALT), requiring regular monitoring.
• Cerebral Hemorrhage: Reported in isolated cases of severe thrombocytopenia.

Research Areas

In the fields of Stem Cell and Regenerative Medicine, CC-90002 is studied for its role in “Phagocytic Clearance.” CD47 is a marker of “self” on Hematopoietic Stem Cells. Researchers use the data from CC-90002 trials to understand how to protect healthy stem cells during cancer treatment. Newer 2026 research is exploring “Bispecific” CD47 antibodies that only bind to cancer cells, leaving the “Don’t Eat Me” signal intact on healthy stem cells, thereby preventing anemia and allowing for safer immune regeneration.

Patient Management and Practical Recommendations

Pre-treatment Tests:

• Baseline CBC with Differential: To monitor for anemia and low platelets.
• Liver Function Tests (LFTs): Essential due to the risk of liver enzyme spikes.
• ADA Screening: (In research settings) to check for pre-existing antibodies that might neutralize the drug.

Precautions:

• Infusion Monitoring: For early-phase trials, patients were often hospitalized for 72 hours following the first dose to monitor for severe reactions.
• Platelet Support: Patients with counts below 50 \times 10^9/L may require transfusions before receiving CD47-targeting agents.

“Do’s and Don’ts” List:

• DO report any “shaking chills” or dizziness during the infusion immediately.
• DO watch for signs of bleeding (bruising, nosebleeds), as this drug can lower platelets.
• DON’T ignore sudden shortness of breath; it could be a sign of an infusion reaction or fluid in the lungs.
• DON’T assume this drug is a “standard” treatment; it is currently only relevant as a case study for future immunotherapy design.

Legal Disclaimer

The information provided is for educational and informational purposes only and does not constitute medical advice. CC-90002 is a discontinued investigational agent and is not currently approved by the US Food and Drug Administration (FDA) for any indication. Always consult with a qualified hematologist-oncologist regarding currently available and approved treatments for leukemia, lymphoma, or solid tumors.