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. 1982 Sep;79(17):5384–5387. doi: 10.1073/pnas.79.17.5384

Protection against syngeneic lymphoma by a long-lived cytotoxic T-cell clone.

M O Dailey, E Pillemer, I L Weissman
PMCID: PMC346901  PMID: 6982472

Abstract

The effect of a cloned T-cell line on the in vivo growth of syngeneic lymphoma cells was studied. 1E4 is an H-2-restricted cytotoxic T-cell clone that efficiently kills Abelson virus-induced lymphoma target cells (L1-2) at low effector/target ratios, as measured by in vitro cytotoxicity assays. In addition, it is long lived in vitro in the absence of stimulation and survives for more than 1 wk in vivo in the absence of exogenous antigen or growth factors. Mice injected intraperitoneally with lethal doses of L1-2 and then treated with 1E4 survived longer than animals treated with saline or with a control T-cell clone. Multiple weekly injections of effector cells, or a single injection in animals given a low dose of tumor cells, resulted in 50-80% long-term survivors. The observation that intravenous injection of killer cells was less effective than intraperitoneal treatment, coupled with the previous demonstration of markedly abnormal circulatory patterns for T-cell clones, suggests that those animals succumbing to progressively growing neoplasm die because the effector cells are unable to home into peripheral sites of tumor deposition. Thus, although this cytotoxic T-cell clone does have useful in vivo activity, its function may be partially limited by a generalized defect in migration.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berendt M. J., North R. J. T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med. 1980 Jan 1;151(1):69–80. doi: 10.1084/jem.151.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borberg H., Oettgen H. F., Choudry K., Beattie E. J., Jr Inhibition of established transplants of chemically induced sarcomas in syngeneic mice by lymphocytes from immunized donors. Int J Cancer. 1972 Nov;10(3):539–547. doi: 10.1002/ijc.2910100312. [DOI] [PubMed] [Google Scholar]
  3. Brunner K. T., MacDonald H. R., Cerottini J. C. Quantitation and clonal isolation of cytolytic T lymphocyte precursors selectively infiltrating murine sarcoma virus-induced tumors. J Exp Med. 1981 Aug 1;154(2):362–373. doi: 10.1084/jem.154.2.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cheever M. A., Greenberg P. D., Fefer A., Gillis S. Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2. J Exp Med. 1982 Apr 1;155(4):968–980. doi: 10.1084/jem.155.4.968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cheever M. A., Greenberg P. D., Fefer A. Specific adoptive therapy of established leukemia with syngeneic lymphocytes sequentially immunized in vivo and in vitro and nonspecifically expanded by culture with Interleukin 2. J Immunol. 1981 Apr;126(4):1318–1322. [PubMed] [Google Scholar]
  6. Dailey M. O., Fathman C. G., Butcher E. C., Pillemer E., Weissman I. Abnormal migration of T lymphocyte clones. J Immunol. 1982 May;128(5):2134–2136. [PubMed] [Google Scholar]
  7. Dye E. S., North R. J. T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases. J Exp Med. 1981 Oct 1;154(4):1033–1042. doi: 10.1084/jem.154.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FOLEY E. J. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res. 1953 Dec;13(12):835–837. [PubMed] [Google Scholar]
  9. Fernandez-Cruz E., Gilman S. C., Feldman J. D. Immunotherapy of a chemically-induced sarcoma in rats: characterization of the effector T cell subset and nature of suppression. J Immunol. 1982 Mar;128(3):1112–1117. [PubMed] [Google Scholar]
  10. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  11. Greenberg P. D., Cheever M. A., Fefer A. Detection of early and delayed antitumor effects following curative adoptive chemoimmunotherapy of established leukemia. Cancer Res. 1980 Dec;40(12):4428–4432. [PubMed] [Google Scholar]
  12. Greenberg P. D., Cheever M. A., Fefer A. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes. J Exp Med. 1981 Sep 1;154(3):952–963. doi: 10.1084/jem.154.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hewitt H. B., Blake E. R., Walder A. S. A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin. Br J Cancer. 1976 Mar;33(3):241–259. doi: 10.1038/bjc.1976.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hollander N., Pillemer E., Weissman I. L. Blocking effect of lyt-2 antibodies on T cell functions. J Exp Med. 1980 Sep 1;152(3):674–687. doi: 10.1084/jem.152.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mulé J. J., Forstrom J. W., George E., Hellström I., Hellström K. E. Production of T-cell lines with inhibitory or stimulatory activity against syngeneic tumors in vivo. A preliminary report. Int J Cancer. 1981 Nov 15;28(5):611–614. doi: 10.1002/ijc.2910280513. [DOI] [PubMed] [Google Scholar]
  16. PREHN R. T., MAIN J. M. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957 Jun;18(6):769–778. [PubMed] [Google Scholar]
  17. Prehn R. T., Lappé M. A. An immunostimulation theory of tumor development. Transplant Rev. 1971;7:26–54. doi: 10.1111/j.1600-065x.1971.tb00462.x. [DOI] [PubMed] [Google Scholar]
  18. Rosenberg S. A., Terry W. D. Passive immunotherapy of cancer in animals and man. Adv Cancer Res. 1977;25:323–388. doi: 10.1016/s0065-230x(08)60637-5. [DOI] [PubMed] [Google Scholar]
  19. Schreier M. H., Iscove N. N., Tees R., Aarden L., von Boehmer H. Clones of killer and helper T cells: growth requirements, specificity and retention of function in long-term culture. Immunol Rev. 1980;51:315–336. doi: 10.1111/j.1600-065x.1980.tb00326.x. [DOI] [PubMed] [Google Scholar]
  20. Siegler R., Zajdel S. Pathogenesis of Abelson-virus-induced murine leukemia. J Natl Cancer Inst. 1972 Jan;48(1):189–218. [PubMed] [Google Scholar]

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