BIODISTRIBUTION AND HISTOLOGICAL LOCALIZATION OF ANTI-HUMAN COLON CANCER MONOCLONAL-ANTIBODY (MAB) 1A3 - THE INFLUENCE OF ADMINISTERED MAB DOSE ON TUMOR UPTAKE
BIODISTRIBUTION AND HISTOLOGICAL LOCALIZATION OF ANTI-HUMAN COLON CANCER MONOCLONAL-ANTIBODY (MAB) 1A3 - THE INFLUENCE OF ADMINISTERED MAB DOSE ON TUMOR UPTAKE
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DOI：
10.1002/ijc.2910440614
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发表时间：
1989-12-15
影响因子：
6.4
通讯作者：
CONNETT, JM
中科院分区：
文献类型：
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作者：
FENWICK, JR;PHILPOTT, GW;CONNETT, JM
使用鼠单克隆抗体MAb 1A 3和MOPC-21抗体作为非特异性对照，我们检测了增加125 I标记的MAb剂量（5 μ g至2，000 μ g）对肿瘤定位的影响，所述鼠单克隆抗体MAb 1A 3与发现在人结肠癌中富集的脂质抗原结合。在具有小GW-39人结肠癌肿瘤的仓鼠中的生物分布研究[0.44g . ±. 0.014（SEM）]证明当使用大剂量MAb 1A 3时，肿瘤中抗原结合位点的功能饱和。每克肿瘤的注射剂量结合百分比（ID/g肿瘤）对于完整MAb 1A 3 ≤ 10 mg的剂量保持恒定。100 μ g的剂量，但随着剂量> 100 μ g而降低，表明抗原结合位点的群体已经饱和。虽然对于> 100 μ g的MAb 1A 3剂量，ID/g肿瘤百分比降低，但特异性结合的绝对量/g肿瘤增加（高达1，000 μ g剂量），表明另一群较难接近的1A 3抗原可以继续结合MAb 1A 3。相比之下，MOPC显示相对恒定的ID/g肿瘤百分比（2.26% ± 0.01%）。0.11），比MAb 1A 3（6.8% ± 0.11）低2-3倍。0.14）。这些数据表明，肿瘤结合位点的特异性饱和是一个双相现象。血液和正常组织未显示结合动力学，表明饱和。使用MAb 1A 3 F（ab）2片段（5 μ g至1，000 μ g）的剂量反应实验的结果与使用完整MAb 1A 3获得的结果接近，但与先前使用MAb 1A 3和其它MAb F（ab“）2片段的研究中一样，ID/g肿瘤、血液和非肿瘤组织的百分比较低。组织学检查表明，MOPC或MAb IA 3与肿瘤或正常组织的非特异性结合具有如此低的亲和力，以至于在组织学程序后基本上检测不到。相反，MAb 1A 3（而不是MOPC）在所有剂量下均显示出与肿瘤而非正常组织的特异性细胞结合模式。
Using a murine monoclonal antibody MAb 1A3, which binds to a lipid antigen found enriched in human colon cancer, and MOPC-21 antibody, as a non-specific control, we examined the effect of increasing doses of 125I-labelled MAbs (5 .mu.g to 2,000 .mu.g) on tumor localization. Biodistribution studies in hamsters with small GW-39 human colon carcinoma tumors [0.44g .+-. 0.014 (SEM)] demonstrated functional saturation of antigen binding sites in tumors when large doses of MAb 1A3 were used. The percentage injected dose bound per gram of tumor (ID/g tumor) remained constant for doses of intact MAb 1A3 .ltoreq. 100 .mu.g but decreased with doses > 100 .mu.g, suggesting that a population of antigen binding sites had been saturated. While the percentage ID/g tumor decreased for doses of MAb 1A3 > 100 .mu.g, the absolute amount specifically bound/g tumor increased (up to the 1,000 .mu.g dose), suggesting that another population of less accessible 1A3 antigen could continue to bind MAb 1A3. In contrast, MOPC demonstrated a relatively constant percentage ID/g of tumor (2.26% .+-. 0.11) throughout the dose range which was 2-3 times lower than MAb 1A3 (6.8% .+-. 0.14) at plateau doses (5-100 .mu.g). These data suggested that specific saturation of tumor binding sites was a biphasic phenomenon. Blood and normal tissues did not show binding kinetics suggesting saturation. Results of dose response experiments using MAb 1A3 F(ab)2 fragments (5 .mu.g to 1,000 .mu.g) closely paralleled those obtained with intact MAb 1A3, but with lower percentages of ID/g tumor, blood and non-tumor tissues as in previous studies with MAb 1A3 and other MAb F(ab'')2 fragments. Histological examinations demonstrated that non-specific binding of MOPC or MAb IA3 to tumor or normal tissues was of such low affinity as to be largely undetected after histological procedures. In contrast, MAb 1A3 (but not MOPC) showed specific cell-binding patterns to tumor but not normal tissues at all doses.