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Published on: September 26, 2011
Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor in
T Crombet1, O Torres, V Rodríguez
1Center of Molecular Immunology, Havana, Cuba. Taniac@ict.cim.sld.cu
Abstract:
High levels of growth factors and their receptors have been demonstrated in human tumors. Gliomas and meningiomas are characterized by overexpression of epidermal growth factor receptor (EGF-R). Ior egf/r3, is a neutralizing murine monoclonal antibody (MAb) against EGF-R, and was generated at the Cuban Institute of Oncology. The antibody recognizes EGF-R with high affinity, inhibiting tyrosine kinase activation. A clinical trial was conducted in brain tumor patients to evaluate toxicity, immunogenicity, and clinical benefit of escalating doses of the antibody. Nine patients with histologically confirmed gliomas or meningiomas, who had active or recurrent disease after receiving conventional treatment, received four intravenous doses of ior egf/r3. Total dosages ranged from 160 to 480 mg. As inclusion criteria, radioimmunoscintigraphy with the same MAb labeled with 99mTechnetium (99mTc) was performed. Immune response against the murine antibody was also evaluated. After four doses of ior egf/r3 MAb, no significant toxicity was found, except in one patient who developed a grade 4 allergic adverse event. This reaction was probably related with previous sensitization to the same MAb and the development of human anti-mouse antibodies (HAMA) response. Despite no major objective antitumor responses, eight patients had stable disease on the 6-month evaluation, and two patients remain alive after four years of MAb therapy.
Insights
This study evaluated Ior egf/r3, a monoclonal antibody targeting epidermal growth factor receptor (EGF-R), in brain tumor patients. The antibody showed manageable toxicity and potential for disease stabilization in gliomas and meningiomas.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Overexpression of epidermal growth factor receptor (EGF-R) is common in gliomas and meningiomas.
- Monoclonal antibodies targeting EGF-R offer a potential therapeutic strategy for brain tumors.
Purpose of the Study:
- To evaluate the toxicity, immunogenicity, and clinical benefit of escalating doses of the neutralizing murine monoclonal antibody (MAb) Ior egf/r3 in brain tumor patients.
- To assess the safety and efficacy of Ior egf/r3 in patients with recurrent or active gliomas and meningiomas.
Main Methods:
- A clinical trial involving nine patients with gliomas or meningiomas receiving four intravenous doses of Ior egf/r3 (160-480 mg total dosage).
- Inclusion criteria included radioimmunoscintigraphy using 99mTechnetium-labeled Ior egf/r3 MAb.
- Evaluation of immune response against the murine antibody, including human anti-mouse antibodies (HAMA) development.
Main Results:
- No significant toxicity was observed, except for one patient experiencing a grade 4 allergic event, possibly due to prior sensitization and HAMA response.
- Eight out of nine patients achieved stable disease at the 6-month evaluation.
- Two patients remained alive four years after initiating MAb therapy, indicating long-term survival benefit.
Conclusions:
- Ior egf/r3 MAb demonstrates a favorable safety profile and potential for disease stabilization in patients with gliomas and meningiomas.
- Further investigation into the immunogenicity and therapeutic potential of Ior egf/r3 in brain tumors is warranted.
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