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Characterization of the a431 tumor xenograft as an invivo model for testing epidermal growth factor-receptor
Abstract:
The A431 tumor Xenograft was characterized as a model to test EGF-receptor antagonists. Removal of the EGF rich submandibular gland from athymic mice, or stimulation of EGF production in the submandibular gland by testosterone administration both failed to influence tumor growth. Infusion of EGF from alzet minipumps raised circulating EGF levels, however, A431 tumor growth was not significantly changed. Treatment on the other hand (IP every 4 days) with a monoclonal to the human EGF receptor (225 antibody) produced a dose (1-0.25 mg/inj) related inhibition of Subcutaneous (s.c.) implanted A431 tumor growth. Long term inhibition (> 114 days) of tumor growth was related to the number of doses of antibody administrated with 9/10 tumors not re-growing after 9 doses of 1 mg/mouse/inj given 4 days apart. A dose related inhibition of A431 tumor growth when implanted under the subrenal capsule (src) was also established for the EGF-receptor antibody and tumor regression was frequently observed with doses greater-than-or-equal-to 0.5mg/mouse/inj. These studies indicate that A431 tumor growth is insensitive to modulation of host EGF but can be inhibited by agents that block the EGF-receptor. The s.c. and src implanted A431 tumor models that have been established will now be used to evaluate the antitumor potential of EGF inhibitors identified from our screening programs.
Insights
This study shows that A431 tumor growth is unaffected by changes in epidermal growth factor (EGF) levels but is inhibited by blocking the EGF receptor with a specific antibody, suggesting a new therapeutic strategy.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- The A431 tumor xenograft model is utilized to investigate epidermal growth factor (EGF) receptor antagonists.
- Host EGF levels, modulated by submandibular gland removal or testosterone stimulation, did not impact tumor growth.
Purpose of the Study:
- To evaluate the efficacy of targeting the EGF receptor in the A431 tumor model.
- To determine if modulating host EGF levels affects tumor progression.
Main Methods:
- Administered EGF via minipumps to assess its effect on tumor growth.
- Treated tumors with a monoclonal antibody against the human EGF receptor (225 antibody) via intraperitoneal injection.
- Implanted tumors subcutaneously (s.c.) and under the subrenal capsule (src) to evaluate antibody efficacy in different microenvironments.
Main Results:
- EGF infusion did not significantly alter A431 tumor growth.
- Treatment with the EGF receptor antibody demonstrated a dose-dependent inhibition of s.c. tumor growth.
- Long-term tumor growth inhibition and regression were observed with repeated doses of the antibody, particularly in the src model.
Conclusions:
- A431 tumor growth is resistant to alterations in host EGF levels.
- Blocking the EGF receptor with a monoclonal antibody effectively inhibits A431 tumor growth.
- Established A431 tumor models (s.c. and src) are suitable for screening EGF inhibitors.
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