2.爱必妥产品知识.ppt

* 根据单克隆抗体结构的不同，有分为以下四种，鼠源的，嵌合型的，人源化的和完全人源型的。黄色部分是和EGFR结合的部位，是鼠源性的；绿色部分是人源性的，产生ADCC(抗体依赖的细胞介导的细胞毒作用）等免疫机制，同时能够降低爱必妥的免疫原性。 * - 爱必妥? (cetuximab) is an IgG1 MAb targeting the EGFR with a high specificity and a higher affinity than either of the two main activating growth factors (EGF and TGF-alpha).[1] - The binding of 爱必妥? to EGFR blocks ligand-induced EGFR signaling and results in the inhibition of proliferation, stimulation of apoptosis, inhibition of angiogenesis, and prevention of metastasis formation.[1] Being an IgG1 MAb, 爱必妥? has been proposed to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro.[2] Therefore, in addition to its inhibitory function on receptor signaling, patients with EGFR-expressing tumors may also benefit from this immune stimulatory effect of 爱必妥?. - The antibody has a long half-life of around 3-4 days, making it suitable for convenient weekly administration. 爱必妥? is administered 400 mg/m2 for the first infusion followed by 250 mg/m2 weekly.[3] - 爱必妥? is well tolerated, lacks the hematologic toxicity [4] commonly associated with a number of anticancer agents, and does not exacerbate the toxicity of the investigated chemotherapeutic drugs.[5] The main side effect is an acne-like rash which generally improves during treatment and which usually does not preclude continued treatment.[6] 1. Baselga J. Eur J Cancer 2001; 37 Suppl 4:S16-S22. 2. Naramura M, Gillies SD, Mendelsohn J, et al. Cancer Immunol Immunother 1993; 37:343-349. 3. 爱必妥? SPC 2004. 4. Mendelsohn J. J Clin Oncol 2002; 20 Suppl 18:1S-13S. 5. Delbaldo C, Pierga JY, Dieras V, et al. Eur J Cancer 2003; 1 Suppl: Abstract 552. 6. Needle MN. Semin Oncol 2002; 29 Suppl 14:55-60. * 伊利替康：喜树碱；阿糖胞苷：吉西他滨；蒽环类：阿霉素 * 很多临床前试验显示了爱必妥与化疗药物或放疗联合应用，对放化疗的増敏作用。 - Non-clinical studies have shown that 爱必妥? has excellent activity in colorectal tumor model systems in vitro and in vivo.[1–4] 爱必妥? induced DiFi colon cancer cells to undergo apoptosis. The apoptosis was associated with the activ