Current Science

Open Access Open Access  Restricted Access Subscription Access

Anti-Tumour and Immune Enhancing Activities of MLAA-22379–387 on Acute Myeloid Leukemia


Affiliations
1 Department of Pediatrics, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
2 Department of Hematology, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
 

We have earlier demonstrated that MLAA-22379–387is a novel, acute, monocytic, leukemia-associated antigen epitope in vitro. In this study, the effect and mechanism of MLAA-22379–387on animals have been further examined. We found that tumour weight and volume had significantly decreased in SCID-injected THP-1 mice with MLAA-22379–387treatment for two weeks. MLAA-22379–387induced cytotoxic T lymphocytes (CTL) activity in A549, MCF-7, THP-1, U937 and T2 cells, especially significant CTL activity at effector/target ratio of 50 : 1 in THP-1 cells. The percentage of CD3 + CD8 + T cells had significantly increased, while the percentage of CD4 + CD25 + T cells had significantly decreased in MLAA-22379–387treatment group compared to other groups. Levels of IL-2, IFN-γand IgG had significantly increased, but levels of TGF-βand IL-10 had significantly decreased after MLAA-22379–387vac-cination for two weeks. Thus, we may conclude that MLAA-22379–387treatment effectively improves the immune system, thus indicating tumouricidal capacity in leukaemic mice. These findings highlight the potential application of MLAA-22379–387 as an efficient target for immunotherapy in acute myeloid leukemia.

Keywords

Acute Myeloid Leukemia, Anti-Tumour Activity, Immunotherapy, Mice.
User
Notifications
Font Size

  • Deschler, B. and Lubbert, M., Acute myeloid leukemia: epidemiology and etiology. Cancer, 2006, 107, 2099–2107.

  • Schlenk, R. F. and Döhner, H., Genomic applications in the clinic: use in treatment paradigm of acute myeloid leukemia. Hematol. Am. Soc. Hematol. Educ. Program., 2013, 1, 324–330.

  • Appelbaum, F. R. et al., Age and acute myeloid leukemia. Blood, 2006, 107, 481–485.

  • Khalil, D. N., Smith, E. L., Brentjens, R. J. and Wolchok, J. D., The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nature Rev. Clin. Oncol., 2016, 13, 273–290.

  • Acheampong, D. O. et al., Immunotherapy for acute myeloid leukemia (AML): a potent alternative therapy. Biomed. Pharmacother., 2018, 97, 225–232.

  • Grosso, D. A., Hess, R. C. and Weiss, M. A., Immunotherapy in acute myeloid leukemia. Cancer, 2015, 121, 2689–2704.

  • Kolb, H. J., Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood, 2008, 112, 4371–4383.

  • Walter, R. B. et al., Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood, 2012, 119, 6198–6208.

  • Schurch, C. M., Riether, C. and Ochsenbein, A. F., Dendritic cell-based immunotherapy for myeloid leukemias. Front. Immunol., 2013, 4, 496.

  • Kobayashi, Y. et al., A new peptide vaccine OCV-501: in vitropharmacology and phase 1 study in patients with acutemyeloid leukemia. Cancer Immunol. Immunother., 2017, 66, 851– 863.

  • Molldrem, J. et al., Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood, 1996, 88, 2450–2457.

  • Greiner, J. et al., Characterization of several leukemia-associated antigens inducing humoral immune responses in acute and chronic myeloid leukemia. Int. J. Cancer, 2013, 106, 224–231.

  • Sohn, H. J. et al., Simultaneous in vitrogeneration of CD8 and CD4 T cells specific to three universal tumour associated antigens of WT1, survivin and TERT and adoptive T cell transfer for the treatment of acute myeloid leukemia. Oncotarget, 2017, 8, 44059– 44072.

  • Zhou, F. L. et al., Bioinformatic analysis and identification for a novel antigen MLAA-22 in acutemonocytic leukemia. J. Exp. He-matol. Chin. Assoc. Pathophysiol., 2008, 16, 466–471.

  • Gu, L. F. et al., Expression and clinical significance of MLAA-22 in acute monocytic leukemia. Mod. Oncol., 2018, 26, 2753–2756.

  • Li, J. et al., Prediction and identification of HLA-A*0201-restricted epitopes from leukemia-associated protein MLAA-22 which elicit cytotoxic T lymphocytes. Med. Oncol., 2014, 31, 293.

  • Sharma, A. et al., Safety and blood sample volume and quality of a refined retro-orbital bleeding technique in rats using a lateral approach. Lab. Anim. (NY), 2014, 43, 63–66.

  • Przespolewski, A., Szeles, A. and Wang, E. S., Advances in immunotherapy for acute myeloid leukemia. Future Oncol., 2018, 14, 963–978.

  • Zhou, Q. et al., Humanized NOD-SCID IL2rg–/– mice as a preclinical model for cancer research and its potential use for individualized cancer therapies. Cancer Lett., 2014, 1, 13–19.

  • Amrita, D. and Debasis, M., Chapter 5 – development of mouse models for cancer research. Anim. Biotechnol., 2014, 73–94.

  • Edward, R. et al., Advances in patient-derived tumor xenografts: from target identification to predicting clinical response rates in oncology. Biochem. Pharmacol., 2014, 2, 135–143.

  • Chua, B. Y. et al., Dendritic cell acquisition of epitope cargo mediated by simple cationic peptide structures. Peptides, 2008, 29, 881–890.

  • Guo, Z. et al., DCs pulsed with novel HLA-A2-restricted CTL epitopes against hepatitis C virus induced a broadly reactive anti-HCV-specific T lymphocyte response. PLoS ONE, 2012, 7, e38390.

  • Lasa, A. et al., WT1 monitoring in core binding factor AML: Comparison with specific chimeric products. Leuk. Res., 2009, 12, 1643–1649.

  • Kim, M. Y. et al., Function of CD4+ CD3– cells in relation to B- and T-zone stroma in spleen. Blood, 2007, 109, 1602–1610.

  • McKinney, D. E. F. et al., Signatures of CD4 T-cell help and CD8 exhaustion predict clinical outcome in autoimmunity, infection, and vaccination. Lancet, 2013, 381, 74.

  • Sakaguchi, S., Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nature Immunol., 2005, 6, 345–352.

  • Son, C. H. et al., Enhancement of antitumor immunity by combination of anti-CTLA-4 antibody and radioimmunotherapy through the suppression of Tregs. Oncol. Lett., 2017, 13, 3781–3786.

  • Liu, J. F. et al., Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer. J. Exp. Clin. Cancer Res., 2018, 37, 44.

  • Yang, Z. Z. et al., Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma.Blood, 2006, 107, 3639–3646.

  • Hope, C. M. et al., The immune phenotype may relate to cancer development in kidney transplant recipients. Kidney Int., 2014, 86, 175–183.

  • Boyman, O. and Sprent, J., The role of interleukin-2 during homeostasis and activation of the immune system. Nature Rev. Immunol., 2012, 12, 180–190.

  • Loria-Cervera, E. N., Cloning and sequence analysis of Peromys-cus yucatanicus(Rodentia) Th1 (IL-12p35, IFN-γand TNF) and Th2 (IL-4, IL-10 and TGF-β) cytokines. Cytokine, 2014, 65, 48– 55.

  • Dunn, G. P., Koebel, C. M. and Schreiber, R. D., Interferons, immunity and cancer immunoediting. Nature Rev. Immunol., 2006, 6, 836–848.

  • Qiu, X. et al., Immunoglobulin gamma heavy chain gene with somatic hypermutation is frequently expressed in acute myeloid leukemia. Leukemia, 2013, 27, 92–99.

  • Mocellin, S., Marincola, F. M. and Young, H. A., Interleukin-10 and the immune response against cancer: a counterpoint. J. Leukocyte Biol., 2005, 78, 1043–1051.

  • Massague, J., TGF beta signalling in context. Nature Rev. Mol. Cell Biol., 2012, 13, 616–630.

  • Massague, J. and Obenauf, A. C., Metastatic colonization by circulating tumour cells. Nature, 2016, 529, 298–306.

  • Kim, J. Y. et al., Inhibition of dextran sulfate sodium (DSS)-induced intestinal inflammation via enhanced IL-10 and TGF-β production by galectin-9 homologues isolated from intestinal parasites. Mol. Biochem. Parasitol., 2010, 174, 53–61.


Abstract Views: 459

PDF Views: 139




  • Anti-Tumour and Immune Enhancing Activities of MLAA-22379–387 on Acute Myeloid Leukemia

Abstract Views: 459  |  PDF Views: 139

Authors

Jing Li
Department of Pediatrics, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
Wanggang Zhang
Department of Hematology, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
Ju Bai
Department of Hematology, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
Bo Zhong
Department of Pediatrics, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
Huiyuan Wang
Department of Pediatrics, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
Yan Geng
Department of Pediatrics, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
Qiaoyan Jin
Department of Pediatrics, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
Juanjuan Hao
Department of Pediatrics, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China
Yang Zhang
Department of Pediatrics, Medical School of Xi’an Jiaotong University, Xi’an Xincheng Xiwu Road 157, Xi’an 710004, Shaanxi Province, China

Abstract


We have earlier demonstrated that MLAA-22379–387is a novel, acute, monocytic, leukemia-associated antigen epitope in vitro. In this study, the effect and mechanism of MLAA-22379–387on animals have been further examined. We found that tumour weight and volume had significantly decreased in SCID-injected THP-1 mice with MLAA-22379–387treatment for two weeks. MLAA-22379–387induced cytotoxic T lymphocytes (CTL) activity in A549, MCF-7, THP-1, U937 and T2 cells, especially significant CTL activity at effector/target ratio of 50 : 1 in THP-1 cells. The percentage of CD3 + CD8 + T cells had significantly increased, while the percentage of CD4 + CD25 + T cells had significantly decreased in MLAA-22379–387treatment group compared to other groups. Levels of IL-2, IFN-γand IgG had significantly increased, but levels of TGF-βand IL-10 had significantly decreased after MLAA-22379–387vac-cination for two weeks. Thus, we may conclude that MLAA-22379–387treatment effectively improves the immune system, thus indicating tumouricidal capacity in leukaemic mice. These findings highlight the potential application of MLAA-22379–387 as an efficient target for immunotherapy in acute myeloid leukemia.

Keywords


Acute Myeloid Leukemia, Anti-Tumour Activity, Immunotherapy, Mice.

References





DOI: https://doi.org/10.18520/cs%2Fv118%2Fi6%2F892-900