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 liters 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.