Chu Thi Thao, Bui Viet Anh, Nguyen Van Phong, Nguyen Trung Kien, Nguyen Dac Tu, Doan Trung Hiep, Nguyen Thanh Liem, Hoang Thi My Nhung

Main Article Content

Abstract

Immunotherapy recently attracted high attention of scientists in cancer treatment. However, this therapy is poorly studied and applied in Vietnam. In this report, we present the results of immune cell ex vivo expansion for cancer treatment. After 20-21 days of culture, the average number of CD3+CD8+ cytotoxic T lymphocytes (CTLs) increased by 633.6-fold, equivalent to 3,277.5 × 106 cells, and with the cell viability of  96.3%. Among them, the increasing folds of lung, liver and gastric cancer patients were 232.4, 812.4 and 655.6, respectively. Meanwhile, the average number of CD3- CD56+ natural killer (NK) cells increased by 940.3-fold, equivalent to 2,659.3 × 106 cells, with the cell viability of 95%. Gastric cancer patients had the highest-fold NK cell expansion (1,644.9-fold) compared to that in lung cancer patients (695.0-fold), and liver cancer patients (358.3-fold). These results revealed that our method of immune cell expansion met the requirements in the immune cell number for clinical applications in cancer treatment in Vietnam.

Keywords: Immune cell therapy, natural killer cells, cytotoxic T lymphocytes, peripheral blood mononuclear cells, cancer.

References

[1] H. Sung, J. Ferlay, R. L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA Cancer J Clin, Vol. 71, No. 3, 2021, pp. 209-249, https://doi.org/10.3322/caac.21660.
[2] G. Delaney, S. Jacob, C. Featherstone, M. Barton, The Role of Radiotherapy in Cancer Treatment: Estimating Optimal Utilization from a Review of Evidence-based Clinical Guidelines, Cancer, Vol. 104, No. 6, 2005, pp. 1129-37, https://doi.org/10.1002/cncr.21324.
[3] M. A. Cheever, C. S. Higano, Provenge (Sipuleucel-T) in Prostate Cancer: the First FDA-Approved Therapeutic Cancer Vaccine, Clin Cancer Res, Vol. 17, No. 11, 2011, pp.3520-3526, http:// doi.org/10.1158/1078-0432.CCR-10-3126.
[4] J. C. Castle, S. Kreiter, J. Diekmann, M. Löwer, N. Van De Roemer, J. De Graaf, A. Selmi, M. Diken, S. Boegel, C.Paret, Exploiting the Mutanome for Tumor Vaccination, Cancer Res, Vol. 72, No. 5, 2012, pp. 1081-1091, http://doi.org/10.1158/0008-5472.CAN-11-3722
[5] A. Hoos, C. M. Britten, C. Huber, J. O’donnell-Tormey, A Methodological Framework to Enhance the Clinical Success of Cancer Immunotherapy, Nat Biotechnol, Vol. 29, No. 10, 2011, pp. 867-870, http://doi.org/ 10.1038/nbt.2000.
[6] J. M. Kirkwood, L. H. Butterfield, A. A. Tarhini, H. Zarour, P. Kalinski, S. Ferrone, Immunotherapy of Cancer in 2012, CA Cancer J Clin, Vol. 62, No. 5, 2012, pp. 309-335, https://doi.org/10.1038/nrurol.2012.106.
[7] H. Terunuma, X. Deng, Z. Dewan, S. Fujimoto, N. Yamamoto, Potential Role of NK Cells in the Induction of Immune Responses: Implications for NK Cell-Based Immunotherapy for Cancers and Viral Infections, Int Rev Immunol, Vol. 27, No. 3, 2008, pp. 93-110, http://doi.org/ 10.1080/08830180801911743.
[8] S. Srivastava, A. Lundqvist, R. W. Childs, Natural Killer Cell Immunotherapy for Cancer: a New Hope, Cytotherapy, Vol. 10, No. 8, 2008, pp. 775-83, http://doi.org/ 10.1080/14653240802648181.
[9] T. Walzer, M. Dalod, S. H. Robbins, L. Zitvogel, E. Vivier, Natural-Killer Cells and Dendritic Cells: “l'Union Fait la Force”, Blood, Vol. 106, No. 7, 2005, pp. 2252-2258, http://doi.org/ 10.1182/blood-2005-03-1154.
[10] J. C. Sun, L. L. Lanier, NK Cell Development, Homeostasis and Function: Parallels with CD8+ T Cells, Nat Rev Immunol, Vol. 11, No. 10, 2011, pp. 645-657, http://doi.org/ 10.1038/nri3044.
[11] H. G. Ljunggren, K. J. Malmberg, Prospects for the Use of NK Cells in Immunotherapy of Human Cancer, Nat Rev Immunol, Vol. 7, No. 5, 2007, pp. 329-339, http://doi.org/ 10.1038/nri2073.
[12] K. Karre, H. G. Ljunggren, G. Piontek, R. Kiessling, Selective Rejection of H-2-Deficient Lymphoma Variants Suggests Alternative Immune Defence Strategy, Nature, Vol. 319, No. 6055, 1986, pp. 675-678, http://doi.org/ 10.1038/319675a0.
[13] S. A. Rosenberg, B. S. Packard, P. M. Aebersold, D. Solomon, S. L. Topalian, S. T. Toy, P. Simon, M. T. Lotze, J.C. Yang, C. A. Seipp, Use of Tumor-Infiltrating Lymphocytes and Interleukin-2 in the Immunotherapy of Patients with Metastatic Melanoma. A Preliminary Report, N. Eng, J. Med, Vol. 319, 1988, pp. 1676-1680, http://doi.org/ 10.1056/NEJM198812223192527.
[14] T. Takayama, T. Sekine, M. Makuuchi, S. Yamasaki, T. Kosuge, J. Yamamoto, K. Shimada, M. Sakamoto, S. Hirohashi, Y. Ohashi, T. Kakizoe, Adoptive Immunotherapy to Lower Postsurgical Recurrence Rates of Hepatocellular Carcinoma: a Randomised Trial, Lancet, Vol. 356. No. 9232, 2000, pp. 802-807, http://doi.org/ 10.1016/S0140-6736(00)02654-4.
[15] K. Iwai, K. Soejima, S. Kudoh, Y. Umezato, T. Kaneko, K. Yoshimori, H. Tokuda, T. Yamaguchi, A. Mizoo, Y. Setoguchi, T. Kamigaki, K. Fujimoto, S. Goto, Extended Survival Observed in Adoptive Activated T Lymphocyte Immunotherapy for Advanced Lung Cancer: Results of a Multicenter Historical Cohort Study, Cancer Immunol Immunother, Vol. 61,
No. 10, 2012, pp. 1781-1790, http://doi.org/ 10.1007/s00262-012-1226-4.
[16] S. Goto, T. Kaneko, Y. Miyamoto, M. Eriguchi, A. Kato, T. Akeyama, K. Fujimoto, M. Tomonaga, K. Egawa, Combined Immunocell Therapy Using Activated Lymphocytes and Monocyte-Derived Dendritic Cells for Malignant Melanoma, Anticancer Res, Vol. 25, No. 6A, 2005, pp. 3741-6.
[17] R. Mocikat, H. Braumuller, A. Gumy, O. Egeter, H. Ziegler, U. Reusch, A. Bubeck, J. Louis,
R. Mailhammer, G. Riethmuller, U. Koszinowski, M. Rocken, Natural Killer Cells Activated by MHC Class I(Low) Targets Prime Dendritic Cells to Induce Protective CD8 T Cell Responses, Immunity, Vol. 19, No. 4, 2003, pp. 561-569, http://doi.org/ 10.1016/s1074-7613(03)00264-4.
[18] J. M. Kelly, P. K. Darcy, J. L. Markby, D. I. Godfrey, K. Takeda, H. Yagita, M. J. Smyth, Induction of Tumor-Specific T Cell Memory by NK Cell-Mediated Tumor Rejection, Nat Immunol, Vol. 3, No. 1, 2002, pp 83-90, http://doi.org/ 10.1038/ni746.
[19] H. Terunuma, X. Deng, N. Nishino, K. Watanabe, N. K Cell-Based Autologous Immune Enhancement Therapy (AIET) for Cancer, J Stem Cells Regen Med, Vol. 9, No. 1, 2013, pp. 9-13, http://doi.org/ 10.46582/jsrm.0901003.
[20] H. Terunuma, Autologous Immune Enhancement Therapy for Cancer - Our Experience Since 2004, J Stem Cells Regen Med, Vol. 8, No. 3, 2012,
pp. 205-206.
[21] T. M. N. Hoang, V. A. Bui, L. H. Truong, T. H. Doan, T. T. Chu, N. L. Phung, T. L. Nguyen, Ex vivo Expansion of Human Peripheral Blood Natural Killer Cells and Cytotoxic T Lymphocytes from Lung Cancer Patients, Oncol Lett, Vol. 15, No. 4, 2018, pp. 5730-573, http://doi.org/ 10.3892/ol.2018.8029.
[22] R. Kananathan, S. Baskar, Chithra, K. Kohila, D. S. Sheela, S. R. Manjunath, V. Abhi, D. Xuewen, H. Terunuma, Autologous Immune Enhancement Therapy Against an Advanced Epithelioid Sarcoma: A Case Report, Oncol Lett, Vol. 5, No. 5, 2013, pp. 1457-1460, http://doi.org/ 10.3892/ol.2013.1247.
[23] S. Premkumar, V. D. Dedeepiya, H. Terunuma, R. Senthilkumar, T. Srinivasan, H. C. Reena, S. Preethy, S. J. Abraham, Cell Based Autologous ImmunefEnhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix, Case Rep Oncol Med, Vol. 903094, 2013, pp. 903094, http://doi.org/ 10.1155/2013/903094.
[24] S. Baskar, R. Kananathan, R. Chithre, K. Kohila, D. S. Sheela, D. Xuewen, H. Terunuma, Autologous Immune Enhancement Therapy: A Case Report of a Stage IV Colonic Cancer, Oncol Lett, Vol. 5, No. 5, 2013, pp. 1611-1614, http://doi.org/ 10.3892/ol.2013.1246.
[25] R. Revathi, M. Deenadayalan, G. Vimal Kumar, K. Vipin, S. Karuna, S. Rajappa, J. K. A. Samuel, H. Terunuma, Autologous Immune Enhancement Therapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia, Indian J Hematol Blood Transfus, Vol. 30 (Suppl 1), 2014, pp. 202-204, http://doi.org/ 10.1007/s12288-013-0327-3.