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Thl Bias in PBAAC induced by large scale auto - CIK infusion in malignant solid tumor patients in China

  • Original Articles
  • Published:
Chinese Journal of Clinical Oncology

Abstract

Objective

This article is to verify feasibility and validity of autologous cytokine-induced killer cell (Auto -CIK) treatment in solid malignancy patients.

Methods

Amplification, phenotypic characteristics, cytokine secretion, antitumor cytotoxicity and clinical response to Auto-CIK derived from 65 cases of solid tumor patients with different pathological types and clinical stages were compared with LAKs in a large-scale clinical trial.

Results

We found that seriousness of disease and metastatic status had no influence on effective components and antitumor immunological activity of Auto-CIK. Comparing cytotoxicity against various tumor cells with LAKs at various effector to target ratios, CIKs showed more effective cytotoxicity against NK sensitive or non-sensitive solid tumor cell lines at a low E/T ratio (6:1) which suggests indirectly that Auto-CIK had a longer effective time in vivo than LAKs. These results suggest that CIKs are more suitable for immunotherapy for those solid malignancy patients at high risk of relapse or recurrence.

Conclusions

Our experimental data were consistent with the reported conclusion that the potent antitumor activity of Auto-CIK mainly rooted in the CD4- part of CIKs, including CD3+CD56+ cells and CD8+ CTLs. The CD4+ part of CIKs seemed to have no direct tumor lytic activity. The results indicate that the special “Th1 bias” and enhanced cytotoxicity against K562 cells occurred in PBMCs after multicycles of Auto-CIK infusions suggesting the induction of a “Th1 shift” and rectification of “Th2 dominance” in PBMC after Auto-C IK treatments.

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References

  1. Schmidt-Wolf GD, Negrin RS, Schmidt-Wolf IG. Activated T cells and cytokine-induced CD3+CD56+ killer cells. Ann Hematol. 1997; 74:51–56.

    Article  PubMed  CAS  Google Scholar 

  2. Margolin KA, Negrin RS, Wong KK, et al. Cellular immunotherapy and autologous transplantation for hematologic malignancy. Immunol Rev. 1997; 157:231–240.

    Article  PubMed  CAS  Google Scholar 

  3. Lu PH, Negrin RS. A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. J Immunol. 1994; 153:1687–1696.

    PubMed  CAS  Google Scholar 

  4. Schmidt-Wolf IG, Lefterova P, Johnston V, et al. Sensitivity of multidrug-resistant tumor cell lines to immunologic effector cells. Cell Immunol. 1996; 169:85–90.

    Article  PubMed  CAS  Google Scholar 

  5. Hoyle C, Bangs CD, Chang P, et al. Expansion of Philadelphia chromosome-negative CD3(+)CD56(+) cytotoxic cells from chronic myeloid leukemia patients: in vitro and in vivo efficacy in severe combined immunodeficiency disease mice. Blood. 1998; 92:3318–3327.

    PubMed  CAS  Google Scholar 

  6. Verneris MR, Kornacker M, Mailander V, et al. Resistance of ex vivo expanded CD3+CD56+ T cells to Fas-mediated apoptosis. Cancer Immunol Immunother. 2000; 49:335–345.

    Article  PubMed  CAS  Google Scholar 

  7. Scheffold C, Brandt K, Johnston V, et al. Potential of autologous immunologie effector cells for bone marrow purging in patients with chronic myeloid leukemia. Bone Marrow Transplant. 1995; 15:33–39.

    PubMed  CAS  Google Scholar 

  8. Muller M, Scheffold C, Lefterova P, et al. Potential of autologous immunologie effector cells for prediction of progression of disease in patients with chronic myelogenous leukemia. Leuk Lymphoma. 1998; 31:335–341.

    PubMed  CAS  Google Scholar 

  9. Linn YC, Lau LC, Hui KM. Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Br J Haematol. 2002; 116:78–86.

    Article  PubMed  CAS  Google Scholar 

  10. Grimm EA, Mazumder A, Zhang HZ, et al. Lymphokine activated killer cell phenomenon: lysis of natural killer resistant fresh solid lymphocytes. J Exp Med. 1982; 155: 1823–1841.

    Article  PubMed  CAS  Google Scholar 

  11. Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor infiltrating lymphocytes. Science. 1986; 233:1318–1321.

    Article  PubMed  CAS  Google Scholar 

  12. Mehta BA, Schmidt-Wolf IG, Weissman IL, et al. Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells. Blood. 1995; 86:3493–3499.

    PubMed  CAS  Google Scholar 

  13. Schmidt-Wolf IG, Finke S, Trojaneck B, et al. Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma. Br J Cancer. 1999; 81:1009–1116.

    Article  PubMed  CAS  Google Scholar 

  14. Mori T, Takada R, Watanabe R, et al. T-helper(Th)l/Th2 imbalance in patients with previously untreated B-cell diffuse large cell lymphoma. Cancer Immunol Immunother. 2001; 50:566–568.

    Article  PubMed  CAS  Google Scholar 

  15. Sato M, Goto S, Kaneko R, et al. Impaired production of Thl cytokines and increased frequency of Th2 subsets in PBMC from advanced cancer patients. Anticancer Res. 1998; 18:3951–3955.

    PubMed  CAS  Google Scholar 

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Authors

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Correspondence to Xiubao Ren.

Additional information

This work was supported by grants from Tianjin Nature Science Fundation (No. 023611011).

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Ren, X., Yu, J., Liu, H. et al. Thl Bias in PBAAC induced by large scale auto - CIK infusion in malignant solid tumor patients in China. Chin. J. Clin. Oncol. 1, 284–294 (2004). https://doi.org/10.1007/BF02739815

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  • DOI: https://doi.org/10.1007/BF02739815

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