A new
severe combined immunodeficiency (SCID) mouse model consisting of highly disseminated human
B-cell leukemia/
lymphoma was developed by i.v. inoculation of BALL-1a, an in vivo adapted malignant B-cell line. A 100% transplantability was achieved in nonpreconditioned SCID mice using various BALL-1a doses between 2.5 x 10(4) and 6 x 10(6) cells. Hind-leg
paralysis preceded the death of the mice. Utility of the developed
tumor model for the therapeutic studies was investigated by i.v. administration of an anti-B-cell
monoclonal antibody SN7 (
IgG1) and its conjugate with deglycosylated
ricin A chain (dgRA). The
therapy was initiated 2, 4, or 6 days after
tumor inoculation using 4 x 24 microg of SN7-dgRA or 4 x 20 microg of SN7; the total dose (96 microg) of SN7-dgRA corresponded to 14% of the LD50 dose. SN7-dgRA showed a strong antitumor efficacy in all groups of treated mice. All of the day-2 group mice (n = 7) and six (66.7%) of the day-4 group mice (n = 9) survived healthily for as long as followed (240 days), whereas four (57.1%) of the day-6 group mice (n = 7) survived healthily for as long as followed (200 days). Unconjugated SN7 showed a significant antitumor efficacy but was less effective than SN7-dgRA. A PCR-based assay specific for the clonogenic BALL-1a
tumor was developed and applied to determine
tumors in various organs of BALL-1a-bearing SCID mice. The assay was highly sensitive in screening for trace quantities of
residual tumors in various organs of SCID mice, and it could detect 1 malignant cell/2.5 x 10(5) tissue cells. The PCR-based assay was shown to be much more powerful than the conventional histological analysis in detecting
residual tumors. Furthermore, we could estimate quantities of the detected
tumors by the PCR-based assay. It is remarkable to find that all examined organs of some of the SN7-dgRA-treated mice were
tumor-free as determined by the clonotype-specific PCR-based assay. The present results show the usefulness of the newly developed SCID mouse model, SN7-dgRA, and the clonotype-specific PCR-based molecular assay for the study of
therapy of human
B-cell leukemia/
lymphoma.