Stein R, Chen S, Sharkey R M, Goldenberg D M
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry, Newark, New Jersey 07103.
Cancer Res. 1990 Feb 15;50(4):1330-6.
The tumor targeting properties of murine monoclonal antibodies (MAbs) generated in our laboratory against non-small cell carcinoma of the lung have been investigated in nude mouse xenograft models. The MAbs selected for evaluation, RS5-4H6, RS7-3G11, and R511-51, have pancarcinoma reactivity, as shown by immunoperoxidase staining of the majority of tumors from the lung as well as breast, colon, kidney, and ovary. The localization of the three MAbs which bind to distinct antigens, and exhibit different levels of cross-reactivity with normal human epithelial tissues, are compared. The MAbs are of the IgG1 isotype. Since these MAbs were reactive with Calu-3, a human adenocarcinoma of the lung cell line grown as xenografts in nude mice, this system was selected as our initial tumor target. The MAbs were found to localize preferentially to the heterotransplanted tumors, with from 6.6 to 8.6% of the injected dose per gram accreting in the tumor at 7 days. Tumor/nontumor ratios of up to 9.7 were seen with one MAb at day 14. The targeting of MAb RS11-51 and F(ab')2 fragments of RS11-51 in GW-39, a human colon cancer grown in nude mice, was also studied. Accretion of intact RS11-51 and F(ab')2 fragments into GW-39 was greatly increased compared to Calu-3. In view of the high frequency of antigen expression on a wide variety of tumors, and the ability to target in vivo, these new MAbs may have potential use in the imaging and therapy of cancer.
我们实验室制备的针对非小细胞肺癌的鼠单克隆抗体（MAb）的肿瘤靶向特性已在裸鼠异种移植模型中进行了研究。选择用于评估的单克隆抗体RS5-4H6、RS7-3G11和R511-51具有泛癌反应性，如对来自肺以及乳腺、结肠、肾和卵巢的大多数肿瘤进行免疫过氧化物酶染色所示。比较了三种与不同抗原结合且与正常人上皮组织表现出不同程度交叉反应性的单克隆抗体的定位情况。这些单克隆抗体为IgG1同种型。由于这些单克隆抗体与Calu-3有反应，Calu-3是一种在裸鼠中异种移植生长的人肺腺癌细胞系，因此该系统被选为我们最初的肿瘤靶点。发现这些单克隆抗体优先定位于异种移植肿瘤，在第7天时每克肿瘤摄取的注射剂量为6.6%至8.6%。在第14天时，一种单克隆抗体的肿瘤/非肿瘤比值高达9.7。还研究了单克隆抗体RS11-51及其F(ab')2片段在裸鼠中生长的人结肠癌GW-39中的靶向情况。与Calu-3相比，完整的RS11-51和F(ab')2片段在GW-39中的摄取量大大增加。鉴于多种肿瘤上抗原表达的高频率以及体内靶向能力，这些新的单克隆抗体可能在癌症成像和治疗中具有潜在用途。
