Zhu Z, Ghose T, Hoskin D, Lee C L, Fernandez L A, Lee S H, Mammen M
Department of Pathology, Dalhousie University, Nova Scotia, Canada.
Cancer Res. 1994 Oct 1;54(19):5111-7.
After i.v. or i.p. inoculation of 5 x 10(6) D10-1 cells, a subclone of an Epstein-Barr virus transformed human B-cell chronic lymphocytic leukemia (CLL) line, 100% of nude mice developed solid or ascites tumors and died within 17-60 days of tumor inoculation. There was significant tumor inhibition, including tumor cure, when these tumor-inoculated mice were treated with either unmodified or 131I (300 microCi)-linked Dal B02 (50 micrograms/mouse), a monoclonal antibody directed against surface-associated antigens on human CLL B-cells and several histological types of B-lymphoma cells. There was no significant difference between the antitumor activity of unmodified Dal B02 and 131I-linked Dal B02 when the treatment was given 3 days after i.p. or i.v. inoculation of 5 x 10(6) D10-1 cells. However, when the mice were treated 3 days after i.p. inoculation of 15 x 10(6) D10-1 cells, or 7 days after the i.v. inoculation of 5 x 10(6) D10-1 cells, 131I-linked Dal B02 was a more potent tumor inhibitor than was unmodified Dal B02 (P < 0.05 and P < 0.01, respectively). Two injections of 131I (500 microCi) linked to 100 micrograms of a Dal B02 F(ab')2 fragment preparation also prolonged the survival of i.p. or i.v. tumor-inoculated mice (P < 0.05 and P = 0.05, respectively). In nude mice with established s.c. xenografts of D10-1 cells, two injections of 131I (300 microCi) linked to 50 micrograms of Dal B02 led to complete tumor cure in 3 of 4, mice, but two injections of 50 micrograms of unmodified Dal B02 had no effect on the s.c. xenografts. Two injections of 131I (500 microCI) linked to 100 micrograms of Dal B02 F(ab')2 fragment caused significant tumor inhibition but no tumor cure. 131I (300 microCi) linked to 50 micrograms of a nonspecific IgG1 only led to minor tumor inhibition. A mixture of unmodified Dal B02 and 131I-linked nonspecific IgG1 was not a more potent tumor inhibitor than the 131I-linked nonspecific IgG1 preparation by itself. These results suggest that Dal B02 may be an effective carrier for the radioimmunotherapy of human B-cell CLL and other appropriate B-cell lymphomas, especially in the progressive phase of B-cell CLL, which is usually not amenable to currently available therapeutic modalities.
静脉注射或腹腔接种5×10⁶个D10 - 1细胞（一种爱泼斯坦 - 巴尔病毒转化的人B细胞慢性淋巴细胞白血病（CLL）系的亚克隆）后，100%的裸鼠出现实体瘤或腹水瘤，并在接种肿瘤后的17 - 60天内死亡。当用未修饰的或¹³¹I（300微居里）连接的Dal B02（50微克/只小鼠）治疗这些接种肿瘤的小鼠时，出现了显著的肿瘤抑制，包括肿瘤治愈，Dal B02是一种针对人CLL B细胞和几种组织学类型的B淋巴瘤细胞表面相关抗原的单克隆抗体。在腹腔注射或静脉注射5×10⁶个D10 - 1细胞3天后进行治疗时，未修饰的Dal B02和¹³¹I连接的Dal B02的抗肿瘤活性没有显著差异。然而，当在腹腔注射15×10⁶个D10 - 1细胞3天后或静脉注射5×10⁶个D10 - 1细胞7天后对小鼠进行治疗时，¹³¹I连接的Dal B02比未修饰的Dal B02是更有效的肿瘤抑制剂（分别为P < 0.05和P < 0.01）。两次注射与100微克Dal B02 F(ab')₂片段制剂连接的¹³¹I（500微居里）也延长了腹腔或静脉接种肿瘤小鼠的生存期（分别为P < 0.05和P = 0.05）。在已建立D10 - 1细胞皮下异种移植物的裸鼠中，两次注射与50微克Dal B02连接的¹³¹I（300微居里）导致4只小鼠中的3只肿瘤完全治愈，但两次注射50微克未修饰的Dal B02对皮下异种移植物没有影响。两次注射与100微克Dal B02 F(ab')₂片段连接的¹³¹I（500微居里）引起显著的肿瘤抑制但没有肿瘤治愈。与50微克非特异性IgG1连接的¹³¹I（300微居里）仅导致轻微的肿瘤抑制。未修饰的Dal B02和¹³¹I连接的非特异性IgG1的混合物并不比¹³¹I连接的非特异性IgG1制剂本身更有效地抑制肿瘤。这些结果表明，Dal B02可能是用于人B细胞CLL和其他合适的B细胞淋巴瘤放射免疫治疗的有效载体，特别是在通常不适合现有治疗方式的B细胞CLL进展期。
