Reid I, Lundy J, Monson J, Nelson H, Ramsay P, Ilstrup D, Donohue J
Department of Surgery, Mayo Clinic, Rochester, Minnesota 55905.
Br J Surg. 1992 Jul;79(7):628-32. doi: 10.1002/bjs.1800790710.
Covalent linkage of an antitumour antibody specific for a tumour cell surface antigen to an antilymphocyte antibody specific for the T lymphocyte receptor complex produces a heteroconjugated antibody that can activate and redirect cytotoxic T lymphocytes to lyse tumour cells. The ability of an antilymphocyte-antitumour heteroconjugate (500A2 x 96.5) to direct the lysis of murine melanoma cells by cultured murine lymphocytes was tested in vitro using a 4-h chromium release assay and in vivo with a tumour neutralization assay. In vitro, the addition of heteroconjugated antibody significantly increased tumour lysis by murine C3H/HeN lymphocytes (median specific lysis 82.7 per cent with lymphocytes plus heteroconjugate versus 9.5 per cent for lymphocytes alone, P less than 0.001). In vivo, treatment with heteroconjugated antibody plus lymphocytes significantly reduced the development of pulmonary metastases after intravenous tumour administration (median number of pulmonary metastases 28.5 for combined treatment versus 250 for heteroconjugate or lymphocytes alone, P less than 0.001).
将针对肿瘤细胞表面抗原的抗肿瘤抗体与针对T淋巴细胞受体复合物的抗淋巴细胞抗体共价连接，可产生一种异源共轭抗体，该抗体能够激活细胞毒性T淋巴细胞并使其重新定向裂解肿瘤细胞。利用4小时铬释放试验在体外以及通过肿瘤中和试验在体内测试了抗淋巴细胞 - 抗肿瘤异源共轭物（500A2×96.5）引导培养的鼠淋巴细胞裂解鼠黑色素瘤细胞的能力。在体外，添加异源共轭抗体显著增加了鼠C3H/HeN淋巴细胞对肿瘤的裂解作用（淋巴细胞加异源共轭物时的中位特异性裂解率为82.7%，而单独淋巴细胞时为9.5%，P<0.001）。在体内，静脉注射肿瘤后，用异源共轭抗体加淋巴细胞治疗显著减少了肺转移瘤的发生（联合治疗时肺转移瘤的中位数量为28.5，而异源共轭物或单独淋巴细胞治疗时为250，P<0.001）。
