In:
International Journal of Cancer, Wiley, Vol. 56, No. 3 ( 1994-02), p. 439-445
Abstract:
To establish xenograft models of human B‐cell chronic lymphocytic leukemia (CLL), we inoculated S × 10 6 D 10‐1 cells, a subline of Epstein‐Barr virus (EBV)‐transformed human B‐cell CLL with a marker chromosomal anomaly, into SCID or irradiated nude mice by the intravenous (i.v.) or intraperitoneal (i.p.) route. All i.p. tumor‐inoculated mice developed rapidly progressive, lethal ascites tumor, and 100% of i.v. tumor‐inoculated mice developed disseminated CLL. All mice died of tumor within 8 weeks of tumor inoculation. Tumor‐inoculated SCID mice died earlier with wider tumor dissemination than the tumor‐inoculated nude mice. All the tumor‐inoculated mice had histologically confirmed metastases in lymph nodes, and most of them also had metastases in one or more internal organs. Cytogenetic analysis confirmed the origin of these tumors from the xenografted D 10‐1 cells. The D 10‐1 cells harvested from the xenografts did not differ from the parent D 10‐1 cells as regards (i) reactivity with 2 monoclonal antibodies (MAbs) directed against CLL‐associated cell‐surface antigens; (ii) rate of proliferation in vitro ; and (Hi) sensitivity to the 2 chemotherapeutic agents, methotrexate and adriamycin. Administration of 50 μg/mouse of Dal B02, an IgG 1 (K) MAb directed against surface‐associated antigens of human B‐cell CLL, significantly prolonged the survival of D 10‐1 ‐inoculated nude and SCID mice. The MAb was more effective in D 10‐1 ‐inoculated nude mice than in SCID mice. In all the D 10‐1 xenograft models, the effectiveness of Dal B02 decreased with higher tumor load but increased with the amount of MAb injected. Dal B02 F(ab)' 2 fragment failed to demonstrate any anti‐tumor activity in D 10‐1 ‐inoculated nude mice. In vttro assays revealed that Dal B02 had no direct inhibitory effect on D 10‐1 cells, but could be cytotoxic towards D 10‐1 cells in the presence of splenic cells or peritoneal macrophages from nude and SCID mice, or together with rabbit complement.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
DOI:
10.1002/ijc.2910560326
Language:
English
Publisher:
Wiley
Publication Date:
1994
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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