Paradoxical enhancement of tumor growth in mice with severe combined immunodeficiency which produce a human immunoglobulin G reactive against tumor cells.

Mice with severe combined immunodeficiency reconstituted with human splenic tissue (SCID-sp) taken from 22 patients with advanced gastric cancer and 8 with idiopathic thrombocytopenic purpura (ITP) received subsequent implants of COLO 205 human colon cancer cells. A human immunoglobulin G (IgG) reactive against COLO 205 cells (COLO 205-reactive human IgG) was produced by SCID-sp mice reconstituted with splenic tissue from 8 of the 22 gastric cancer patients, but from none of the ITP patients. Tumor growth in SCID-sp mice which produced the COLO 205-reactive human IgG was greater (tumor weight range, 106-143%) than that in the control SCID mice, while that in SCID-sp mice reconstituted with splenic tissue from 8 ITP patients and that in SCID-sp mice reconstituted with splenic tissue from the other 14 gastric cancer patients which did not produce the COLO 205-reactive IgG were considerably lower and slightly lower, respectively, than those in the control SCID mice (tumor weight range, 56.7-108% and 79.4-119%, respectively). When the COLO 205-reactive human IgG titers in the sera of the SCID-sp mice, expressed as a ratio of the titers in the corresponding patient's serum, were plotted against the tumor weight in each SCID-sp mouse, significant correlations were observed in those that received splenic tissues from 6 of the 8 patients in which the COLO 205-reactive human IgG was produced. Furthermore, the tumor growth rates increased in proportion to the increased COLO 205-reactive human IgG titers in SCID-sp mice. Therefore, the SCID-sp model should be useful to study the paradoxical tumor growth possibly due to impaired immune reaction in patients with advanced gastric cancer.