In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2

P. J. Spiess, J. C. Yang, S. A. Rosenberg

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

A method was described for the generation of cells from tumor-bearing mice; these cells were capable of exhibiting significant antitumor reactivity when adoptively transferred into tumor-bearing hosts. Tumor cell suspensions from a variety of tumors were able to be separated using enzymatic techniques and they were cultured in medium containing recombinant interleukin-2. Activated infiltrating lymphocytes within these tumors expanded; and, by 6-8 days after initiation of culture, lymphocytes predominated and were able to grow to large numbers. The adoptive transfer of these tumor-infiltrating lymphocytes (TILs) made possible mediation of the reduction of established 3-day pulmonary micrometastases from 5 of 7 tumors tested, including two 3- methylcholanthrene (CAS: 56-49-5)-induced sarcomas, one 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon carcinoma, and the B16 melanoma, all in C57BL/6 mice, as well as the 1660 bladder carcinoma in BALB/c mice. Approximately 2-4x106 transferred cells were capable of totally eliminating 3-day established metastases. These cells were thus 50 to 100 times more effective than lymphokine-activated killer cells in reducing established metastases; however, they could not be generated from all tumors. The concomitant administration of recombinant interleukin-2 enhanced, by approximately fivefold, the in vivo activity of these cells. The specificity of action of TILs in vivo was different from that determined by classic amputation rechallenge experiments. The tumor-infiltrating lymphocytes that developed this antitumor reactivity appeared to be Thy-1+ and did not bear the asialo G(M1) antigen. The potent antitumor effect of these TILs, when transferred in vivo to tumor-bearing hosts, raises the possibility of utilizing similar approaches for the isolation and therapeutic use of lymphocytes with antitumor reactivity from human tumors.

Original languageEnglish (US)
Title of host publicationJournal of the National Cancer Institute
Pages1067-1075
Number of pages9
Volume79
Edition5
StatePublished - 1987
Externally publishedYes

Fingerprint

Tumor-Infiltrating Lymphocytes
Interleukin-2
Neoplasms
Methylcholanthrene
Lymphocytes
1,2-Dimethylhydrazine
Neoplasm Metastasis
Carcinoma
Lymphokine-Activated Killer Cells
Neoplasm Micrometastasis
Experimental Melanomas
Adoptive Transfer
Therapeutic Uses
Inbred C57BL Mouse
Amputation
Sarcoma
Suspensions
Colon
Urinary Bladder
Antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Spiess, P. J., Yang, J. C., & Rosenberg, S. A. (1987). In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. In Journal of the National Cancer Institute (5 ed., Vol. 79, pp. 1067-1075)

In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. / Spiess, P. J.; Yang, J. C.; Rosenberg, S. A.

Journal of the National Cancer Institute. Vol. 79 5. ed. 1987. p. 1067-1075.

Research output: Chapter in Book/Report/Conference proceedingChapter

Spiess, PJ, Yang, JC & Rosenberg, SA 1987, In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. in Journal of the National Cancer Institute. 5 edn, vol. 79, pp. 1067-1075.
Spiess PJ, Yang JC, Rosenberg SA. In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. In Journal of the National Cancer Institute. 5 ed. Vol. 79. 1987. p. 1067-1075
Spiess, P. J. ; Yang, J. C. ; Rosenberg, S. A. / In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. Journal of the National Cancer Institute. Vol. 79 5. ed. 1987. pp. 1067-1075
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