Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy.

摘要: A fully human IgG2kappa monoclonal antibody (MAb), E7.6.3, specific to the epidermal growth factor (EGF) receptor (EGFr) was generated from antibody-producing XenoMouse strains engineered be deficient in mouse production and contain majority of gene repertoire on megabase-sized fragments heavy kappa light chain loci. The E7.6.3 MAb exhibits high affinity (KD = 5 x 10(-11) M) receptor, blocks completely binding both EGF transforming alpha (TGF-a) various EGFr-expressing carcinoma cell lines, abolishes EGF-dependent activation, including EGFr tyrosine phosphorylation, increased extracellular acidification rate, proliferation. (0.2 mg i.p. twice a week for 3 weeks) prevents formation epidermoid A431 xenografts athymic mice. More importantly, administration without concomitant chemotherapy results complete eradication established tumors as large 1.2 cm3. Tumor achieved nearly all mice treated with total doses low mg, administered over course weeks, dose 0.6 led tumor elimination 65% No recurrence observed more than 8 months after last injection, which further indicated by antibody. potency eradicating well-established indicates its potential monotherapeutic agent treatment multiple solid tumors, those no effective is available. Being antibody, expected exhibit minimal immunogenicity longer half-life compared or mouse-derivatized MAbs, thus allowing repeated administration, immunocompetent patients. These suggest good candidate assessing full therapeutic anti-EGFr therapy patient populations tumors.