Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1994 Sep;83(1):45–51.

Adoptive immunotherapy mediated by anti-TCR/IL-2-activated tumour-draining lymph node cells.

S Mitsuma 1, H Yoshizawa 1, K Ito 1, H Moriyama 1, M Wakabayashi 1, T Chou 1, M Arakawa 1, S Shu 1
PMCID: PMC1414996  PMID: 7821965

Abstract

The adoptive immunotherapy of cancer with sensitized T lymphocytes is well documented in several animal models. These studies indicate the existence of precursor lymphocytes, in the tumour-bearing animals, which can acquire therapeutic efficacy after in vitro manipulations. To generate immune effector cells, these precursor lymphocytes have to be antigenically stimulated in vitro by the tumour of origin. Using the weakly immunogenic MCA 205 and MCA 203 murine sarcomas, we demonstrate here that this in vitro antigenic stimulation can be achieved by sequential activation with anti-T-cell receptor (TCR) monoclonal antibody and interleukin-2 (IL-2). The culture of tumour-draining lymph node (TDLN) cells with anti-TCR/IL-2 resulted in an up to eightfold increase in cell numbers. The adoptive transfer of these activated cells mediated a significant reduction of 3-day established pulmonary metastases. Although this antibody could activate all of the TCR alpha beta-bearing T cells non-specifically, the therapeutic efficacy mediated by anti-TCR/IL-2-activated cells was tumour specific. Treatment of MCA 205 advanced pulmonary metastases resulted in prolongation of survival, and 30% of treated mice were tumour free for more than 90 days. These tumour-free mice rejected a challenge of MCA 205 but not MCA 203, indicating the development of long-lasting systemic tumour immunity. In spite of their in vivo anti-tumour efficacy, the anti-TCR/IL-2-activated TDLN cells did not exhibit detectable in vitro cytotoxicity. These results demonstrate that this activation method could be an alternative way to generating potent anti-tumour effector T cells.

Full text

PDF
45

Selected References

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

  1. Barth R. J., Jr, Bock S. N., Mulé J. J., Rosenberg S. A. Unique murine tumor-associated antigens identified by tumor infiltrating lymphocytes. J Immunol. 1990 Feb 15;144(4):1531–1537. [PubMed] [Google Scholar]
  2. Chang A. E., Yoshizawa H., Sakai K., Cameron M. J., Sondak V. K., Shu S. Clinical observations on adoptive immunotherapy with vaccine-primed T-lymphocytes secondarily sensitized to tumor in vitro. Cancer Res. 1993 Mar 1;53(5):1043–1050. [PubMed] [Google Scholar]
  3. Cheever M. A., Greenberg P. D., Fefer A. Potential for specific cancer therapy with immune T lymphocytes. J Biol Response Mod. 1984;3(2):113–127. [PubMed] [Google Scholar]
  4. Chou T., Chang A. E., Shu S. Y. Generation of therapeutic T lymphocytes from tumor-bearing mice by in vitro sensitization. Culture requirements and characterization of immunologic specificity. J Immunol. 1988 Apr 1;140(7):2453–2461. [PubMed] [Google Scholar]
  5. Fernandez-Cruz E., Halliburton B., Feldman J. D. In vivo elimination by specific effector cells of an established syngeneic rat moloney virus-induced sarcoma. J Immunol. 1979 Oct;123(4):1772–1777. [PubMed] [Google Scholar]
  6. Frank S. J., Niklinska B. B., Orloff D. G., Merćep M., Ashwell J. D., Klausner R. D. Structural mutations of the T cell receptor zeta chain and its role in T cell activation. Science. 1990 Jul 13;249(4965):174–177. doi: 10.1126/science.2371564. [DOI] [PubMed] [Google Scholar]
  7. GEHAN E. A. A GENERALIZED WILCOXON TEST FOR COMPARING ARBITRARILY SINGLY-CENSORED SAMPLES. Biometrika. 1965 Jun;52:203–223. [PubMed] [Google Scholar]
  8. Gallinger S., Hoskin D. W., Mullen J. B., Wong A. H., Roder J. C. Comparison of cellular immunotherapies and anti-CD3 in the treatment of MCA-38-LD experimental hepatic metastases in C57BL/6 mice. Cancer Res. 1990 Apr 15;50(8):2476–2480. [PubMed] [Google Scholar]
  9. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  10. Loeffler C. M., Platt J. L., Anderson P. M., Katsanis E., Ochoa J. B., Urba W. J., Longo D. L., Leonard A. S., Ochoa A. C. Antitumor effects of interleukin 2 liposomes and anti-CD3-stimulated T-cells against murine MCA-38 hepatic metastasis. Cancer Res. 1991 Apr 15;51(8):2127–2132. [PubMed] [Google Scholar]
  11. Minami Y., Samelson L. E., Klausner R. D. Internalization and cycling of the T cell antigen receptor. Role of protein kinase C. J Biol Chem. 1987 Sep 25;262(27):13342–13347. [PubMed] [Google Scholar]
  12. Rosenberg S. A., Grimm E. A., McGrogan M., Doyle M., Kawasaki E., Koths K., Mark D. F. Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science. 1984 Mar 30;223(4643):1412–1414. doi: 10.1126/science.6367046. [DOI] [PubMed] [Google Scholar]
  13. Rosenberg S. A., Packard B. S., Aebersold P. M., Solomon D., Topalian S. L., Toy S. T., Simon P., Lotze M. T., Yang J. C., Seipp C. A. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988 Dec 22;319(25):1676–1680. doi: 10.1056/NEJM198812223192527. [DOI] [PubMed] [Google Scholar]
  14. Rosenberg S. A., Spiess P., Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986 Sep 19;233(4770):1318–1321. doi: 10.1126/science.3489291. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Shu S. Y., Chou T., Rosenberg S. A. Generation from tumor-bearing mice of lymphocytes with in vivo therapeutic efficacy. J Immunol. 1987 Jul 1;139(1):295–304. [PubMed] [Google Scholar]
  17. Smith H. G., Harmel R. P., Hanna M. G., Jr, Zwilling B. S., Zbar B., Rapp H. J. Regression of established intradermal tumors and lymph node metastases in guinea pigs after systemic transfer of immune lymphoid cells. J Natl Cancer Inst. 1977 May;58(5):1315–1322. doi: 10.1093/jnci/58.5.1315. [DOI] [PubMed] [Google Scholar]
  18. Ting C. C., Hargrove M. E., Yun Y. S. Augmentation by anti-T3 antibody of the lymphokine-activated killer cell-mediated cytotoxicity. J Immunol. 1988 Aug 1;141(3):741–748. [PubMed] [Google Scholar]
  19. Van Wauwe J., Goossens J. Mitogenic actions of Orthoclone OKT3 on human peripheral blood lymphocytes: effects of monocytes and serum components. Int J Immunopharmacol. 1981;3(3):203–208. doi: 10.1016/0192-0561(81)90014-x. [DOI] [PubMed] [Google Scholar]
  20. Wexler H. Accurate identification of experimental pulmonary metastases. J Natl Cancer Inst. 1966 Apr;36(4):641–645. doi: 10.1093/jnci/36.4.641. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES