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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Jan;85(1):72–79. doi: 10.1111/j.1349-7006.1994.tb02888.x

Paradoxical Enhancement of Tumor Growth in Mice with Severe Combined Immunodeficiency which Produce a Human Immunoglobulin G Reactive against Tumor Cells

Toshiharu Furukawa 1, Masahiko Watanabe 1, Tetsuro Kubota 1,, Masaki Kitajima 1
PMCID: PMC5919332  PMID: 8106291

Abstract

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.

Keywords: SCID mouse, Human immunoglobulin G, Splenic tissue

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REFERENCES

  • 1. ) Bosma , G. C. , Custer , R. P. and Bosma , M. J.A severe combined immunodeficiency mutation in the mouse . Nature , 301 , 527 – 530 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) McCune , J. M. , Namikawa , R. , Kaneshima , H. , Shultz , L. D. , Lieberman , M. and Weissman , I. L.The SCID‐hu mouse: murine model for the analysis of human hemato‐lymphoid differentiation and function . Science , 241 , 1632 – 1639 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Mosier , D. E. , Gulizia , R. J. , Baird , S. M. and Wilson , D. B.Transfer of a functional human immune system to mice with severe combined immunodeficiency . Nature , 335 , 256 – 259 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Duchosal , M. A. , Eming , S. A. , Fischer , P. , Leturcq , D. , BarbasIII , C. F. , McConahey , P. J. , Caothien , R. H. , Thornton , G. B. , Dixon , F. J. and Burton , D. R.Immunization of hu‐PBL‐SCID mice and the rescue of human monoclonal Fab fragments through combinatorial libraries . Nature , 355 , 258 – 262 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Kubota , T. , Yamaguchi , H. , Watanabe , M. , Yamamoto , T. , Takahara , T. , Takeuchi , T. , Furukawa , T. , Kase , S. , Kodaira , S. , Ishibiki , K. and Kitajima , M.High human IgG levels in severe combined immunodencient mouse reconstituted with human splenic tissues from patients with gastric cancer . Jpn. J. Cancer Res. , 83 , 300 – 303 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. ) Furukawa , T. , Watanabe , M. , Kubota , T. , Yamaguchi , H. , Teramoto , T. , Ishibiki , K. and Kitajima , M.Production of human immunoglobulin G reactive against human cancer in tumor‐bearing mice with severe combined immunodeficiency reconstituted with human splenic tissues . Jpn. J. Cancer Res. , 83 , 894 – 898 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Marson , L. A.Does antibody‐dependent epitope masking permit progressive tumour growth in the face of cell‐mediated cytotoxicity ? Immunol. Today , 12 , 352 – 355 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Hirsch , R. , Eckhaus , M. , Auchincloss , H. , Jr. , Sachs , D. H , and Bluestone , J. A.Effects of in vivo administration of anti‐T3 monoclonal antibody on T cell function in mice . J Immunol. , 140 , 3766 – 3772 ( 1988. ). [PubMed] [Google Scholar]
  • 9. ) Kumazawa , H. and Hess , M.Influence of serum derived from patients with head and neck cancer on natural killer cell activity . Oncology , 48 , 372 – 376 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Semple , T. U. , Quinn , L. A. , Woods , L. K. and Moore , G. E.Tumor and lymphoid cell lines from a patient with carcinoma of the colon for a cytotoxicity model . Cancer Res. , 38 , 1345 – 1355 ( 1978. ). [PubMed] [Google Scholar]
  • 11. ) Japanese Research Society for Gastric Cancer . The general rules for gastric cancer study in surgery and pathology . Jpn. J. Surg. , 11 , 127 – 145 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Dorshkind , K. , Pollack , S. B. , Bosma , M. J , and Phillips , R. A.Natural killer (NK) cells are present in mice with severe combined immunodeficiency (scid) . J. Immunol. , 134 , 3798 – 3801 ( 1985. ). [PubMed] [Google Scholar]
  • 13. ) Murphy , W. J. , Kumar , V. and Bennett , M.Rejection of bone marrow allografts by mice with severe combined immune deficiency (SCID). Evidence that natural killer cells can mediate the specificity of marrow graft rejection . J. Exp. Med. , 165 , 1212 – 1217 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Simpton , E. , Farrant , J. and Chandler , P.Phenotypic and functional studies of human peripheral blood lymphocytes engrafted in scid mice . Immunol. Rev. , 124 , 97 – 111 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Kaneshima , H. , Braum , C. , Chen , B. , Namikawa , R. , Outzen , H. , Rabin , L. , Tsukamoto , A. and McCune , J. M.Today's SCID‐hu mouse . Nature , 348 , 561 – 562 ( 1990. ). [DOI] [PubMed] [Google Scholar]

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