The
therapeutic effects of the low and high affinity mAbs 17-1A and 323/A3 were investigated in nude mice xenografted with LS 180 human
colorectal carcinoma cells. Treatment of mice grafted with dispersed
tumor cells, before formation of a
tumor nodule, was started 1 day after s.c. injection of
tumor cells and consisted of a single i.p. injection of murine 17-1A or 323/A3 mAb.
Tumor appearance after a single injection of either 17-1A or 323/A3 was delayed as compared to injection of an irrelevant mAb. Both 17-1A and 323/A3 reduced the
tumor growth rate, and both mAbs decreased the total number of mice that eventually developed a
tumor. In all experiments, 323/A3 showed consistently better treatment effects on xenografted mice than
mAb 17-1A. For treatment of established
tumors with
mAb 17-1A or 323/A3
therapy was delayed until a
tumor nodule was macroscopically detectable. One single i.p. injection of
mAb 17-1A had no effect on further
tumor growth and mean
tumor size as compared to the control group injected with irrelevant mAb. One single i.p. injection with mAb 323/A3 reduced the
tumor growth rate in some mice with established
tumors and resulted in a significant difference of mean
tumor size of this group as compared to the 17-1A treated mice and the control groups. Multiple
injections with
mAb 17-1A also had no effects on established
tumors, in contrast to mAb 323/A3, where serial
injections resulted in
tumor growth reduction and, eventually, in some mice reduction in
tumor size. In summary, we showed that in nude mice mAb 323/A3 (Ka = 2 x 10(9) M-1) is much more potent than
mAb 17-1A (Ka = 5 x 10(7) M-1) in eradication of nonestablished
tumor cells and treatment of small established
tumors. These results suggest that high affinity mAbs like 323/A3 might dramatically improve the clinical results obtained thus far with the low affinity
mAb 17-1A in the adjuvant treatment of surgically resected Dukes C
colorectal cancer patients with
minimal residual disease.