Juweid M, Sharkey R M, Markowitz A, Behr T, Swayne L C, Dunn R, Hansen H J, Shevitz J, Leung S O, Rubin A D
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Newark, New Jersey 07103, USA.
Cancer Res. 1995 Dec 1;55(23 Suppl):5899s-5907s.
LL2 is a murine IgG2a anti-CD22 monoclonal antibody found to react with virtually all non-Hodgkin's lymphomas (NHLs). Twenty-one patients with chemotherapy-resistant NHL received nonmyeloablative doses of 131I-labeled LL2 IgG and F(ab')2 ranging from 15 to 343 mCi given in cycles of 15-50 mCi, for up to seven treatment cycles. The cumulative protein dose ranged from 1.1 mg IgG to 157 mg F(ab')2. Seventeen patients were assessable for treatment response, and antitumor effects were seen in five (one complete remission, two partial remissions, and two minor or mixed responses). In addition, one complete response was seen in a patient who received only "diagnostic" doses of 131I-LL2 IgG. Thus, a total of six patients had responses according to the defined response criteria. Three additional patients have been treated with potentially myeloablative doses of 131I-LL2 IgG at a starting dose level of 90 mCi/m2 (100 mg). Two patients were evaluable, and both had partial remissions lasting 8 and 3 months, respectively. Chimeric and complementarity-determining region-grafted LL2 have been developed. Initial clinical studies have shown that these agents have targeting properties similar to the murine LL2 and, therefore, may be suitable alternatives to murine LL2 in the treatment of NHL. LL2 is a promising agent for the treatment of lymphoma, particularly when the maximum tolerated dose is given either with or without autologous bone marrow transplantation.
LL2是一种鼠源IgG2a抗CD22单克隆抗体,发现它几乎能与所有非霍奇金淋巴瘤(NHL)发生反应。21例化疗耐药的NHL患者接受了非清髓剂量的131I标记的LL2 IgG和F(ab')2,剂量范围为15至343 mCi,以15 - 50 mCi的周期给药,最多进行七个治疗7个治疗周期。累积蛋白剂量范围为1.1 mg IgG至157 mg F(ab')2。17例患者可评估治疗反应,其中5例出现抗肿瘤效应(1例完全缓解、2例部分缓解以及2例轻微或混合反应)。此外,1例仅接受“诊断性”剂量131I - LL2 IgG的患者出现了完全缓解。因此,根据既定的反应标准,共有6例患者有反应。另外3例患者接受了起始剂量为90 mCi/m2(100 mg)的潜在清髓剂量的131I - LL2 IgG治疗。2例患者可评估,均出现了部分缓解,持续时间分别为8个月和3个月。已开发出嵌合型和互补决定区移植型LL2。初步临床研究表明,这些药物具有与鼠源LL2相似的靶向特性,因此在NHL治疗中可能是鼠源LL2的合适替代物。LL2是一种有前景的淋巴瘤治疗药物,特别是在给予最大耐受剂量时,无论是否进行自体骨髓移植。