The persistence of human peripheral lymphocytes, tumor infiltrating lymphocytes, and colon adenocarcinomas in immunodeficient mice

Douglas L. Jicha, John R. Yannelli, Mary Custer, Jean Colandrea, Jeff Taubenberger, James J. Mulé, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

The reconstitution of severely immunodeficient mice with human peripheral blood mononuclear cells (PBMCs) may represent a unique model system to evaluate human antitumor responses. To evaluate this possibility, we studied human PBMC reconstitution, human tumor infiltrating lymphocyte (TIL) persistence, and human colon adenocarcinoma propagation in beige/nude/xid (BNX) and in severe combined immunodeficient (SCID) mice. To evaluate human PBMC reconstitution, 75 mice received 1 x 107-1 x 109human PBMCs i.p. or i.v. and were studied at intervals ranging from 1 to 8 weeks by fluorescence-activated cell sorting (FACS) analysis and by measurement of circulating human immunoglobulin levels. By FACS analyses, only one of 75 mice had evidence of human PBMC persistence at 2 weeks in the spleen. Moreover, liver and peritoneum showed evidence of human cells in only 13 of 56 and 16 of 55 mice, respectively. In these mice, human cells comprised 1–77% of total cells recovered. Human immunoglobulin levels in mouse serum ranged from 0 to 34,000 μg/ml and correlated only weakly with evidence of human PBMC reconstitution in peripheral organs, but were generally higher in SCID mice than in BNX mice. Human TIL persistence was evaluated in BNX and SCID mice that were given 3 x 107TILs i.v. (in divided doses) or 1 x 108i.p. TILs along with interleukin-2 administration. At 1, 2, 7, and 14 days following TIL delivery, evidence of human TIL persistence in liver, lung, peritoneum, and spleen was evaluated by FACS analysis. Fresh organ suspensions did not contain human TILs. In mice given cyclophosphamide followed by human TILs i.p., the TILs were demonstrated at 7 days in the SCID peritoneum (leu 4 = 4%) and at 2 days in the SCID spleen (leu 4 = 2%). In BNX mice, 12 of 14 fresh human colon adenocarcinomas were propagated successfully at subcutaneous sites with latency periods ranging from 1 to 13 weeks. Enzymatic disaggregation of tumors >1 cm following one passage yielded 6.5–47 x 106cells with viabilities ranging from 13 to 85%. We conclude that limitations and variability exist in the use of BNX and SCID mice for human PBMC reconstitution, TIL persistence, and propagation of human colon adenocarcinomas.

Original languageEnglish (US)
Pages (from-to)19-29
Number of pages11
JournalJournal of Immunotherapy
Volume11
Issue number1
DOIs
StatePublished - Jan 1992

Keywords

  • Human colon adenocarcinomas.
  • Immunodeficient mice
  • Peripheral blood mononuclear cells
  • Tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Jicha, D. L., Yannelli, J. R., Custer, M., Colandrea, J., Taubenberger, J., Mulé, J. J., & Rosenberg, S. A. (1992). The persistence of human peripheral lymphocytes, tumor infiltrating lymphocytes, and colon adenocarcinomas in immunodeficient mice. Journal of Immunotherapy, 11(1), 19-29. https://doi.org/10.1097/00002371-199201000-00003