Nivolumab
[CAS# 946414-94-4]

Identification

• Classification: API >> Antineoplastic agents >> Other antineoplastic agents
• Name: Nivolumab
• Synonyms: BMS 936558; MDX 1106; ONO 4538; Opdivo
• Molecular Weight: ~143620
• CAS Registry Number: 946414-94-4

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

Nivolumab is a fully human monoclonal antibody developed as an immune checkpoint inhibitor targeting the programmed cell death protein 1 (PD-1) receptor. Its discovery arose from research into immune evasion mechanisms employed by cancer cells, which utilize PD-1 signaling to suppress T-cell activity and avoid immune-mediated destruction. By blocking PD-1, nivolumab restores T-cell function and enhances the immune system’s ability to recognize and attack tumor cells.

Nivolumab was developed through a process of antibody engineering and humanization to ensure high specificity for PD-1 with reduced immunogenicity in patients. It belongs to the immunoglobulin G4 (IgG4) subclass, which minimizes antibody-dependent cellular cytotoxicity, thus primarily acting by preventing the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade releases the “brakes” on T cells, allowing a more robust antitumor immune response.

The clinical application of nivolumab began with its approval for the treatment of advanced melanoma, where it showed significant improvements in overall survival compared to standard therapies. Its success in melanoma paved the way for further approvals across various cancer types, including non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, urothelial carcinoma, and others. Nivolumab has become a cornerstone of cancer immunotherapy, often used as monotherapy or in combination with other agents such as ipilimumab, a CTLA-4 inhibitor.

In therapeutic use, nivolumab is administered via intravenous infusion with dosing schedules tailored to the cancer type and patient condition. The drug’s efficacy is closely linked to the presence of PD-L1 expression on tumor or immune cells, although benefits have been observed even in patients with low or absent PD-L1 levels. This has driven the development of companion diagnostic tests to guide treatment decisions.

Nivolumab’s side effect profile includes immune-related adverse events resulting from enhanced immune activity, such as inflammation of organs including the lungs (pneumonitis), intestines (colitis), liver (hepatitis), and endocrine glands (thyroiditis, hypophysitis). These adverse effects require careful management, often involving corticosteroids or other immunosuppressants to control excessive immune reactions while maintaining antitumor efficacy.

The discovery of nivolumab has transformed cancer treatment paradigms by demonstrating the potential of immune checkpoint blockade. It has spurred extensive research into combinations with chemotherapy, targeted therapies, and other immunomodulators to improve outcomes further. Additionally, nivolumab is being investigated in earlier stages of disease and in adjuvant settings to reduce recurrence risk.

Nivolumab’s development reflects the translation of fundamental immunology into clinical application, offering durable responses and survival benefits in cancers with historically poor prognosis. Its approval and widespread use mark a significant advancement in personalized medicine and immuno-oncology.