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Monoclonal antibodies for cancer therapy
1Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Israel.
Abstract:
Monoclonal antibodies directed at tumor-associated antigens have been used clinically since 1981. In most of the completed clinical trials, the McAbs were of murine origin. Twenty-six of 184 patients (14%) receiving McAbs demonstrated a major clinical response, including 3 complete responders. Toxicities are primarily related to immune responses. The immune response triggering the toxic manifestations may be mediated by interactions between the administered McAb and the target tumor-associated antigens, or between the McAb and host antibodies made in response to its administration. Analysis of the mechanism of action, pharmacokinetics and toxicity of McAb administration should lead to improved design of clinical protocols, and provide a basis for the use of human McAbs and McAbs conjugated to radioisotopes, toxins or chemotherapeutic agents.
Insights
Monoclonal antibodies (McAbs) targeting tumor antigens show clinical efficacy, with 14% of patients responding. Understanding McAb immune responses and toxicity is crucial for developing improved cancer therapies.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Monoclonal antibodies (McAbs) targeting tumor-associated antigens have been in clinical use since 1981.
- Most early clinical trials utilized murine-derived McAbs.
Purpose of the Study:
- To review the clinical efficacy and toxicities of McAb therapy.
- To explore the mechanisms underlying McAb-induced toxicities.
- To inform future development of improved McAb-based cancer treatments.
Main Methods:
- Clinical trial data analysis.
- Review of McAb mechanism of action, pharmacokinetics, and toxicity.
- Exploration of immune response mechanisms related to McAb administration.
Main Results:
- A major clinical response rate of 14% (26/184 patients) was observed, including 3 complete responders.
- Toxicities were predominantly linked to host immune responses against the McAbs.
- Immune responses may involve interactions between the McAb and tumor antigens or host antibodies.
Conclusions:
- Analysis of McAb action, pharmacokinetics, and toxicity is essential for optimizing clinical protocols.
- Further research should focus on humanized McAbs and antibody conjugates for enhanced therapeutic strategies.