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Autologous tumor cell killing activity of tumor-associated lymphocytes in patients with head and neck carcinomas

  • Research Articles
  • Published:
Biotherapy

Abstract

In order to select the most cytotoxic effector cells for adoptive immunotherapy, lymphokine activated killer (LAK) cells, tumor infiltrating lymphocytes (TILs) and autologous mixed lymphocyte tumor cell culture (MLTC) cells derived from peripheral blood mononuclear cells (PBMC) in the same subject with head and neck carcinomas were prepared. The autologous tumor cell killing activity and cell surface phenotypes of each of the three effector cells were studied. MLTC cells cultured with interleukin-2 (IL-2) showed the strongest cytotoxic activity among these three different effector cells. Although TILs had suppressed killing activity immediately after isolation, after successive cultivations with IL-2, a cytotoxic activity against autologous tumor cells stronger than that of LAK cells appeared. Both IL-2 stimulated MLTC cells and TILs showed an enrichment of CD8 positive and CDU negative cells in a CD3 positive subpopulation.

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Abbreviations

CD:

cluster differentiation

IL-2:

interleukin-2

LA:

lymphokine activated

LAK:

lymphokine activated killer

MLTC:

mixed lymphocyte tumor cell culture

NK:

natural killer

PBMC:

peripheral blood mononuclear cells

TILs:

tumor infiltrating lymphocytes

References

  1. Rosenberg SA, Lotze ML, Muul LA, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Eng J Med 1987; 316: 889–97.

    Google Scholar 

  2. Rosenberg SA, Packard BS, Aebersold PM, Solomon D. Topalianm SL, Toy ST, Simon P, Lotze MT, Yang JG, Seipp CA, Simpson C, Carter C, Bock S, Schwartzentruber D, Wei JP, White DE. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma, a preliminary report. N Eng J Med 1988: 319: 1676–80.

    Google Scholar 

  3. Lotze MT. The treatment of patients with melanoma using interleukin-2, interleukin-4 and tumor infiltrating lymphocytes. Human Gene Therapy 1992: 3: 167–177.

    PubMed  Google Scholar 

  4. Kriegel RL, Padavic-Schaller KA, Rudolf AR, Litwin S, Konrad M, Bradley EC, Comis RL. A phase I study of recombinant interleukin-2 plus recombinantβ — interferon. Cancer Res 1988; 48: 3875–3881.

    PubMed  Google Scholar 

  5. Budd GT, Osgood B, Barna B, Boyett JM, Finke J, Medendorp SV, Novak C, Sergi J, Tubbs R, Bukowski RM. Phase I clinical trial of interleukin 2 andα — interferon: toxicity and immunologic effects. Cancer Res 1989; 49: 6432–6436.

    PubMed  Google Scholar 

  6. Rubin JT, Elwood LJ, Rosenberg SA, Lotze MT. Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. Cancer Res 1989; 49: 7086–7092.

    PubMed  Google Scholar 

  7. Heo DS, Whiteside TL, Johnson JT, Chen K, Barnes EL, Herberman RB. Long-term interleukin 2-dependent growth head cytotoxic activity of tumor-infiltrating lymphocytes from human squamous cell carcinomas of the head and neck. Cancer Res 1987; 47: 6353–6362.

    PubMed  Google Scholar 

  8. Sawaki S. Treatment of head and neck cancer with recombinant interleukin-2. BIOTHERAPY 1989; 3: 984–988 (in Japanese).

    Google Scholar 

  9. Lindemann A, Hoffken K, Schmidt RE, Diehl V, Kloke O, Gamm H, Hayungs J, Oster W, Bohm M, Kolitz JE, Franks CR, Herrman F, Mertelsmann H. A phase II study of low-dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma. Cancer Immunol Immunother 1989; 28: 275–281.

    PubMed  Google Scholar 

  10. Itoh K, Tilden AB, Balch CM. Interleukin 2 activation of cytotoxic T-lymphocytes infiltrating into human metastatic melanomas. Cancer Res 1986; 46: 3011–3017.

    PubMed  Google Scholar 

  11. Robinowich H, Cohen R, Bruderman I, Steiner Z, Klajan A. Functional analysis of mononuclear cells infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocyte. Cancer Res 1987; 47: 173–177.

    PubMed  Google Scholar 

  12. Whiteside TL, Heo DS, Takagi S, Johnson JT, Iwatsuki S, Herbermann RB. Cytolytic antitumor effector cells in long-term cultures of human tumor-infiltrating lymphocytes in recombinant interleukin-2. Cancer Immunol Immunother 1988: 26: 1–10.

    PubMed  Google Scholar 

  13. Yoo YK, Heo DS, Hata K, Van Thiel DH, Whiteside TL. Tumor-infiltrating lymphocytes from human colon carcinomas. Gastroenteology 1990; 98: 259–268.

    Google Scholar 

  14. Dillman RO, Oldham RK, Barth NM. Cohen RJ, Minor DR, Birch R, Yannell JR. Maleckar JR, Sferruzza A, Arnold J, West WH. Continuous interleukin-2 and tumor infiltrating lymphocytes as treatment of advanced melanoma. Cancer 1991; 68:1–8.

    PubMed  Google Scholar 

  15. Bukowski RM, Sharfman W, Murthy S, Rayman P, Tubbs R, Alexander J, Budd GT, Sergi JS, Bauer L, Gibson V, Stanley J, Boyett J, Pontes E, Finke J. Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin 2 in human metastatic renal cell carcinoma. Cancer Res 1991: 51: 4199–4205.

    PubMed  Google Scholar 

  16. Baars JW. Fonk CM, Scheper RJ, Von Blomberg BME. Bril H, Valk P, Pinedo HM, Wagstaff J. Treatment with tumor infiltrating lymphocytes and interleukin-2 in patients with metastatic melanoma: a pilot study. Biotherapy 1992; 4: 289–297.

    PubMed  Google Scholar 

  17. Salmeron MA, Morita T, Seki H, Platsoucas CD, Itoh K. Lymphokine production by human melanoma tumor-infiltrating lymphocytes. Cancer Immunol Immunother 1992; 35: 211–217.

    PubMed  Google Scholar 

  18. Shimizu Y, Weidmann E, Iwatsuki S, Herberman RB, Whiteside TL. Characterization of human autotumorreactive T-cell clones obtained from tumor-infiltrating lymphocytes in liver metastasis of gastric carcinoma. Cancer Res 1991; 51: 6153–6162.

    PubMed  Google Scholar 

  19. Li WY, Lusheng S, Kanbour A, Herberman RB, Whiteside TL. Lymphocyte infiltrating ovarian tumors synergy between tumor necrosisα and interleukin-2 in the generation of CD8+ effectors from tumor infiltrating lymphocytes. Cancer Res 1989: 49: 5979–5985.

    PubMed  Google Scholar 

  20. Kuppner MC, Hamou MF, Bodmer S. Fontana A, Tribolet ND. The glioblastoma-derived T-cell suppressor factor/transforming growth factor beta2 inhibits the generation of lymphokine activated killer (LAK) cells, Int J Cancer 1988; 42; 562–567.

    PubMed  Google Scholar 

  21. Griffth KD, Read EJ, Carrasquillo JA, Carter CS, Yang JC, Fisher B. Aebersold P. Packard BS, Yu MY, Rosenberg SA.In vivo distribution of adoptively transferred Indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma J Natl Cancer Inst 1989; 81: 1709–1717.

    PubMed  Google Scholar 

  22. Cordon-Cardo C, Fuks Z, Drobnjak M, Moreno C, Eissenbach L. Feldman M. Expression of HLA-A, B, C antigens on primary and metastatic tumor cells populations of human carcinomas. Cancer Res 1991; 51: 6372–6380.

    PubMed  Google Scholar 

  23. Sznol M, Clark JW, Smith II JW, Steis RG, Urba WJ, Rubinstein LV. Vandermolen LA. Janik J. Sharfman WH. Fentow RG. Creekmore SP. Kremers R, Coulon K, Hursey J, Beveridge J, Longo DL, Pilot study of interleukin-2 and lymphokine activated killer cells combined with immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a in patients with metastatic melanoma and renal cell carcinoma J Natl Cancer Inst 1992; 84: 929–937.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Otorhinolaryngology. School of Medicine, Yokohama City University, Fukuura 3-9, Kanazawa-ku, Yokohama, 236, Kanagawa, Japan

    Mamoru Tsukuda, Izumi Mochimatsu, Miki Sakumoto, Shigeru Furukawa & Seiichiro Yuyama

  2. Department of Head and Neck Surgery, Kanagawa Cancer Center, Nakao-cho 54-6, Asahi-ku, Yokohama, 241, Kanagawa, Japan

    Shunsuke Yanoma & Akira Kubota

Authors
  1. Mamoru Tsukuda
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  2. Izumi Mochimatsu
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  3. Miki Sakumoto
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  4. Shigeru Furukawa
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  5. Seiichiro Yuyama
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  6. Shunsuke Yanoma
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  7. Akira Kubota
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Tsukuda, M., Mochimatsu, I., Sakumoto, M. et al. Autologous tumor cell killing activity of tumor-associated lymphocytes in patients with head and neck carcinomas. Biotherapy 6, 155–161 (1993). https://doi.org/10.1007/BF01877429

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