Does Immunotherapy Use Monoclonal Antibodies?
Yes, monoclonal antibodies are a primary form of immunotherapy and represent the most widely used immunotherapeutic approach in current cancer treatment. 1, 2
Classification and Definition
Monoclonal antibodies are definitively classified as immunotherapy because they work by modulating the immune system to target disease, either by blocking immune checkpoints to enhance anti-tumor immunity or by directly targeting specific antigens to activate immune effector functions. 2
- Immune checkpoint inhibitors are the prototypical immunotherapy monoclonal antibodies, working by removing brakes on the immune system rather than directly killing cancer cells. 2
- The Society for Immunotherapy of Cancer explicitly refers to monoclonal antibody agents like nivolumab, pembrolizumab, ipilimumab, and atezolizumab as immunotherapy throughout their consensus guidelines. 1, 2
- The Annals of Oncology guidelines state that monoclonal antibodies targeted against immune checkpoint molecules CTLA-4 and PD-1 are now considered a main component of cancer therapy. 1, 2
Currently Approved Immunotherapy Monoclonal Antibodies
Six immune checkpoint inhibitor monoclonal antibodies are FDA-approved for cancer treatment: 1
- Anti-CTLA-4 agents: Ipilimumab (fully human IgG1 mAb approved in 2011 for advanced melanoma) 1, 3
- Anti-PD-1 agents: Pembrolizumab and nivolumab (both engineered IgG4 mAbs approved in 2014) 1, 4
- Anti-PD-L1 agents: Atezolizumab, durvalumab (both engineered IgG1 mAbs with Fc modifications eliminating ADCC), and avelumab (wildtype IgG1 framework with intact ADCC) 1
Mechanism of Action
These monoclonal antibodies function as immunotherapy by blocking inhibitory immune checkpoint pathways and restoring T cell-mediated cytotoxicity: 2, 4
- Nivolumab is a human IgG4 monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. 4
- Ipilimumab blocks CTLA-4 interaction with its ligands, preventing inhibitory signaling cascades that suppress T-cell activation, primarily interfering at the interface between T cells and antigen-presenting dendritic cells. 3
- Combined nivolumab and ipilimumab mediated inhibition results in enhanced T-cell function greater than either antibody alone. 4
Clinical Implications of Monoclonal Antibodies as Immunotherapy
The classification of monoclonal antibodies as immunotherapy has critical clinical implications that distinguish them from traditional chemotherapy: 2
- Unique toxicity profile: These agents cause immune-related adverse events (irAEs) rather than traditional chemotherapy toxicities, requiring different management strategies. 1, 2
- Delayed onset and prolonged duration: Immunotherapy-related irAEs typically have delayed onset and prolonged duration compared to adverse events from chemotherapy. 1
- Incidence varies by agent: Anti-CTLA-4 therapy (ipilimumab) causes irAEs in 60-85% of patients with 10-27% grade 3-4 toxicities, while anti-PD-1 agents have ≤30% incidence of any-grade irAEs. 1
- Management requires immunosuppression: Effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies, typically high-dose corticosteroids. 1, 2
Broader Context
Beyond checkpoint inhibitors, other monoclonal antibody platforms are also considered immunotherapy when they engage immune mechanisms: 1, 2
- Bispecific antibodies used in multiple myeloma are explicitly discussed as immunotherapy with similar toxicity profiles to CAR T-cell therapy due to their immune mechanisms of action. 1
- Monoclonal antibodies represent the next wave of progress in cancer treatment alongside CAR T-cell therapy and other immune-based therapeutic approaches. 1