BACKGROUND: There is evidence of a relationship between epidermal growth factor (EGF) and tumor cell proliferation, such as the overexpression of EGF receptor (EGF-R) in different human tumors, which makes this system an interesting target for cancer treatment. Up to now, passive immunotherapy with monoclonal antibodies against the EGF-R has been assayed in clinics. Our approach consists of active immunotherapy with human EGF (hu-EGF). We conducted a pilot clinical trial to define the safety, toxicity and immunogenicity of vaccination with hu-EGF coupled to a carrier protein. PATIENTS AND METHODS: Ten patients with histologically-proven malignant carcinomas (colon, lung, stomach and prostate) in advanced clinical stages were enrolled. Patients were immunized twice (on days 0 and 15) with hu-EGF linked to either tetanic toxoid (TT, five patients) or P64K Neisseria Meningitidis recombinant protein (P64k, five patients), intradermically, using aluminium hydroxyde as adjuvant. RESULTS: In both groups 60% of patients developed anti-EGF antibody titers without evidence of toxicity. Secondary reactions were very mild, limited to erythema and itching at the site of injection, which disappeared without medication. CONCLUSIONS: We conclude that the proposed vaccination with hu-EGF was well tolerated and that antibody titers against self EGF were developed. The results of this trial may be useful in the design of new clinical trials with higher dose immunization protocols and using more effective adjuvants.
BACKGROUND: There is evidence of a relationship between epidermal growth factor (EGF) and tumor cell proliferation, such as the overexpression of EGF receptor (EGF-R) in different humantumors, which makes this system an interesting target for cancer treatment. Up to now, passive immunotherapy with monoclonal antibodies against the EGF-R has been assayed in clinics. Our approach consists of active immunotherapy with human EGF (hu-EGF). We conducted a pilot clinical trial to define the safety, toxicity and immunogenicity of vaccination with hu-EGF coupled to a carrier protein. PATIENTS AND METHODS: Ten patients with histologically-proven malignant carcinomas (colon, lung, stomach and prostate) in advanced clinical stages were enrolled. Patients were immunized twice (on days 0 and 15) with hu-EGF linked to either tetanic toxoid (TT, five patients) or P64KNeisseria Meningitidis recombinant protein (P64k, five patients), intradermically, using aluminium hydroxyde as adjuvant. RESULTS: In both groups 60% of patients developed anti-EGF antibody titers without evidence of toxicity. Secondary reactions were very mild, limited to erythema and itching at the site of injection, which disappeared without medication. CONCLUSIONS: We conclude that the proposed vaccination with hu-EGF was well tolerated and that antibody titers against self EGF were developed. The results of this trial may be useful in the design of new clinical trials with higher dose immunization protocols and using more effective adjuvants.
Authors: Hauke Winter; Natasja K van den Engel; Margareta Rusan; Nina Schupp; Christian H Poehlein; Hong-Ming Hu; Rudolf A Hatz; Walter J Urba; Karl-Walter Jauch; Bernard A Fox; Dominik Rüttinger Journal: J Thorac Dis Date: 2011-06 Impact factor: 2.895
Authors: Ian D Davis; Weisan Chen; Heather Jackson; Phillip Parente; Mark Shackleton; Wendie Hopkins; Qiyuan Chen; Nektaria Dimopoulos; Tina Luke; Roger Murphy; Andrew M Scott; Eugene Maraskovsky; Grant McArthur; Duncan MacGregor; Sue Sturrock; Tsin Yee Tai; Simon Green; Andrew Cuthbertson; Darryl Maher; Lena Miloradovic; Susan V Mitchell; Gerd Ritter; Achim A Jungbluth; Yao-Tseng Chen; Sacha Gnjatic; Eric W Hoffman; Lloyd J Old; Jonathan S Cebon Journal: Proc Natl Acad Sci U S A Date: 2004-07-13 Impact factor: 11.205