Shrayer D, Bogaars H, Gersten D, Hearing V, Maizel A, Wanebo H
Department of Pathology, Roger Williams Medical Center, Brown University, Providence, Rhode Island 02908.
J Surg Oncol. 1994 Sep;57(1):50-6. doi: 10.1002/jso.2930570114.
A model to study passive humoral immunotherapy of experimental melanoma was generated by subcutaneous injection of B16 F10 murine melanoma cells in the midtail of BALB/C nude (nu/nu) mice. Mice were challenged with melanoma cells pretreated: (1) with complete culture medium, (2) with 10% adjuvant control serum, (3) with 10% anti-fECA (formalinized extracellular antigens) immune serum, or (4) with a monoclonal antibody (mAB H2-3-3) specific for the B700 melanoma-associated antigen. All control mice challenged with melanoma cells pretreated either with culture medium or with medium containing adjuvant control serum (Groups I and II) died during the observation period of 84 days. At day 84, 60% of the mice challenged with melanoma cells pretreated with anti-fECA immune serum (Group III) survived, as did 100% of the mice challenged with cells pretreated with mAb H2-3-3 (Group IV). Injection of melanoma cells pretreated with mAb H2-3-3 was associated with the greatest reduction of subsequent local tumor growth and the lowest number of metastatic lung tumors. The inhibitory effects of immune sera in vivo also correlated with in vitro effects of anti-fECA immune serum and mAb H2-3-3, determined on B16 F10 melanoma target cells using assays for DNA synthesis and antibody dependent cellular cytotoxicity (ADCC). In sum, this nude mouse model for the study of passive humoral immunotherapy of experimental melanoma was utilized to demonstrate significant protective effects against B16 F10 melanoma cell challenge by treatment with anti-fECA immune sera or a melanoma-specific monoclonal antibody.
通过在BALB/C裸(nu/nu)小鼠的尾中部皮下注射B16 F10小鼠黑色素瘤细胞,建立了一种用于研究实验性黑色素瘤被动体液免疫疗法的模型。用以下预处理的黑色素瘤细胞对小鼠进行攻击:(1)用完全培养基;(2)用10%佐剂对照血清;(3)用10%抗fECA(甲醛化细胞外抗原)免疫血清;或(4)用针对B700黑色素瘤相关抗原的单克隆抗体(mAB H2-3-3)。所有用培养基或含佐剂对照血清的培养基预处理的黑色素瘤细胞攻击的对照小鼠(I组和II组)在84天的观察期内死亡。在第84天,用抗fECA免疫血清预处理的黑色素瘤细胞攻击的小鼠中有60%存活(III组),用mAb H2-3-3预处理的细胞攻击的小鼠中有100%存活(IV组)。用mAb H2-3-3预处理的黑色素瘤细胞注射与随后局部肿瘤生长的最大减少和肺转移瘤数量的最低值相关。免疫血清在体内的抑制作用也与抗fECA免疫血清和mAb H2-3-3的体外作用相关,后者是使用DNA合成测定法和抗体依赖性细胞毒性(ADCC)在B16 F10黑色素瘤靶细胞上测定的。总之,这个用于研究实验性黑色素瘤被动体液免疫疗法的裸鼠模型被用来证明用抗fECA免疫血清或黑色素瘤特异性单克隆抗体治疗对B16 F10黑色素瘤细胞攻击具有显著的保护作用。