Abstract
Objective: To improve the preparation of adherent lymphokine-activated killer (A-LAK) cells and study the synergistic anti-tumor effect of phenylacetate (PA) and A-LAK cells. Methods: A-LAK cells were obtained from peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) by using L-phenylalanine methyl ester (PME) to deplete immunosuppressive monocytes. The proliferation of SMMC7721 cell line treated with PA was studied. A-LAK cells were treated with the supernatant of SMMC7721 cells which had been pretreated with PA and the changes of the proliferation and anti-tumor activity of A-LAK cells were investigated. Results: The expansion of A-LAK cells was significantly higher than that of non-adherent LAK (NA-LAK) cells as well as regular LAK cells. The growth of SMMC7721 cells was significantly suppressed by PA. The supernatant of cultured tumor cells intensively suppressed the proliferation and cytotoxicity of A-LAK cells, but the suppressive effect of supernatant treated with PA previously was decreased. Conclusion: A-LAK cells could be simply prepared by using PME, and showed a synergistic anti-tumor effect with the combination of PA.
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References
Ye SL. Biotherapy of tumor. In: Tang ZY. Contemporary oncology [M]. 2nd ed. Shanghai: Shanghai Medical University Press. 2000; 513.
Bremers AJ, Parmiani G. Immunology and immunotherapy of human cancer: present concepts and clinical developments [J]. Crit Rev Oncol Hematol 2000; 34:1.
Cheng JD, Rieger PT, Von-Mehren M, et al. Recent advances in immunotherapy and monoclonal antibody treatment of cancer [J]. Semin Oncol Nurs 2000; 16(4 Suppl 1):2.
Ye SL. Biotherapy of hepatocellular carcinoma. In: Tang ZY, Yu YQ. Primary liver cancer [M]. 2nd ed. Shanghai: Shanghai Scientific and Technical Press. 1999; 382.
Hoffman DM, Gitlitz BJ, Belldegrun A, et al. Adoptive cellular therapy [J]. Semin Oncol 2000; 27:221.
Melden RJ, Whiteside TL, Vujanovic NL, et al. A new approach to generating antitumor effectors for adoptive immunotherapy using human adherent lymphokine-actived killer cells [J]. Cancer Res 1988; 48:3461.
Schwarz RE, Vujanovic NL, Hiserodt JC. Enhanced antimetastatic activity of lymphokine-activated killer cells purified and expanded by their adherence to plastic [J]. Cancer Res 1989; 49:1441.
Koberda J, Przepiorka D, Moser RP, et al. Sequential TNF and TGF-beta regulation of expansion and induction of cytotoxicity in long-term cultures of lymphokine-activated killer cells [J]. Lymphokine Cytokine Res 1994; 13:139.
Boiardi A, Silvani A, Ruffini PA, et al. Loco-reginoal immunotherapy with recombinant interleukin-2 and adherent lymphokine-actived killer cells (A-LAK) in recurrent glioblastoma patients [J]. Cancer Immunol Immunother 1994; 39:193.
Triozzi PL, Aldrich W, Kim J, et al. Biologic effects of the adoptive transfer of cells depleted of monocytes with L-phenylalanine methyl ester [J]. Immunopharmacol 1994; 28:39.
Riberiro-Dias F, Marzagao-Barbuto JA, Sajita M, et al. Discrimination between NK and LAK cytotoxic activicity of murine spleen cells by MTT assay: differential inhibition by PGE2 and EDTA [J]. J Immunol Methods 2000; 241:121.
Pardoll D. T cells and tumors [J]. Nature 2001; 28; 411:1010.
Schwacha MG, Schneider CP, Bland KI, et al. Resistance of macrophages to the suppressive effect of interleukin-10 following thermal injury [J]. Am J Physiol Cell Physiol 2001; 281:C1180.
Sakata T, Iwagami S, Tsarata Y, et al. The role of lipocortin I in macrophage-mediated immunosuppression in tumor-bearing mice [J]. J Immunol 1990; 145:387.
Bergmann L, Schui DK, Brieger J, et al. The inhibition of lymphokine-actived killer cells in acute myeloblastic leukemia is mediated by TGF-β 1 [J]. Exp Hematol 1995; 23:1574.
Hsieh CL, Chen DS, Hwang LH. Tumor-induced immunosuppression: a barrier to immunotherapy of large tumors by cytokine-secreting tumor vaccine [J]. Hum Gene Ther 2000; 11:681.
Han S, Wada RK, Sidell N. Differentiation of human neuroblastoma by phenylacetate is mediated by peroxisome proliferator-activated receptor gamma [J]. Cancer Res 2001; 61:3998.
Vasse M, Thibout D, Paysant J, et al. Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules [J]. Br J Cancer 2001; 84:802.
Thibault A, Samid D, Cooper MR, et al. Phase I study of phenylacetate administered twice daily to patients with cancer [J]. Cancer 1995; 75:2932.
Liu L, Bar-ner M, Weber J, et al. Enhancement of tumor immunogenicity by phenylacetate and derivatives: Changes in surface antigens and tumor-derived immunosuppressive factors [J]. Proc Am Assoc Cancer Res 1994; 35:481.
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Foundation items: This work was supported by a grant from the National 9th Five-Year Program of China (No. 96-906-01-20).
Biography: ZHENG Ning (1970–), candidate for Ph. D of oncology since 1998, graduated from Shanghai Medical University receiving master degree of internal medicine in 1996, majors in biotherapy of cancer.
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Zheng, N., Ye, Sl., Sun, Rx. et al. The effect of phenylacetate on the expansion and cytotoxic activity of adherent lak cells from patients with hepatocellular carcinoma. Chin. J. Cancer Res. 14, 1–4 (2002). https://doi.org/10.1007/s11670-002-0001-z
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DOI: https://doi.org/10.1007/s11670-002-0001-z
Keywords
- Adherent lymphokine-activated killer cells
- phenylacetate
- hepatocellular carcinoma
- phenylalanine methyl ester