Welt S, Mattes M J, Grando R, Thomson T M, Leonard R W, Zanzonico P B, Bigler R E, Yeh S, Oettgen H F, Old L J
Proc Natl Acad Sci U S A. 1987 Jun;84(12):4200-4. doi: 10.1073/pnas.84.12.4200.
Mouse monoclonal antibody TA99 detects a 70-kDa pigmentation-associated glycoprotein in human melanoma cell lines. The antigen cannot be detected on the cell surface by sensitive rosetting techniques or absorption studies, nor can it be detected as a secreted product in culture fluids. Contrary to expectation, 125I-labeled TA99 specifically localized to pigmented human melanoma transplants in nu/nu mice; no localization to nonpigmented melanoma or control tumors was found. Tumor imaging was initially obscured by circulating 125I-labeled TA99 during the first 6 days after antibody injection. With clearance of 125I-labeled TA99 from the blood (half-life, 4-7 days), specific tumor images could be clearly defined by day 13. Due to the persistence of 125I-labeled TA99 at the tumor site (8.9% of the injected dose at 1 week and 4.6% at 8-10 weeks), images were obtainable for up to 10 weeks. At 8-10 weeks, the tumor/blood ratio was 10(4)-10(5), and the tumor/normal tissue ratio ranged from 10(2) to 10(5). In view of these findings, antibodies detecting intracellular antigens may have a role in tumor imaging and therapy.
小鼠单克隆抗体TA99可在人黑色素瘤细胞系中检测到一种70 kDa的色素沉着相关糖蛋白。通过灵敏的玫瑰花结技术或吸收研究无法在细胞表面检测到该抗原,在培养液中也检测不到其作为分泌产物的存在。与预期相反,125I标记的TA99特异性定位于裸鼠体内有色素沉着的人黑色素瘤移植瘤;未发现其定位于无色素沉着的黑色素瘤或对照肿瘤。在注射抗体后的前6天,循环中的125I标记TA99最初使肿瘤成像模糊不清。随着125I标记TA99从血液中清除(半衰期为4 - 7天),到第13天可清晰界定特异性肿瘤图像。由于125I标记TA99在肿瘤部位持续存在(1周时为注射剂量的8.9%,8 - 10周时为4.6%),长达10周均可获得图像。在8 - 10周时,肿瘤/血液比值为(10^4 - 10^5),肿瘤/正常组织比值在(10^2)至(10^5)之间。鉴于这些发现,检测细胞内抗原的抗体可能在肿瘤成像和治疗中发挥作用。