Enhanced antitumor immune response in melanoma tumor model by anti-PD-1 small interference RNA encapsulated in nanoliposomes.
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
13
12
2020
accepted:
23
06
2021
revised:
23
05
2021
pubmed:
4
8
2021
medline:
23
6
2022
entrez:
3
8
2021
Statut:
ppublish
Résumé
Programmed cell death protein-1 (PD-1), as an immune checkpoint molecule, attenuates T-cell activity and induces T-cell exhaustion. Although siRNA has a great potential in cancer immunotherapy, its delivery to target cells is the main limitation of using siRNA. This study aimed to prepare a liposomal formulation as a siRNA carrier to silence PD-1 expression in T cells and investigate it's in vivo antitumor efficacy. The liposomal siRNA was prepared and characterized by size, zeta potential, and biodistribution. Following that, the uptake assay and mRNA silencing were evaluated in vitro at mRNA and protein levels. siRNA-PD-1 (siPD-1)-loaded liposome nanoparticles were injected into B16F0 tumor-bearing mice to evaluate tumor growth, tumor-infiltrating lymphocytes, and survival rate. Liposomal siPD-1 efficiently silenced PD-1 mRNA expression in T cells (P < 0.0001), and siPD-1-loaded liposomal nanoparticles enhanced the infiltration of T-helper 1 (Th 1) and cytotoxic T lymphocytes into the tumor tissue (P < 0.0001). Liposome-PD-1 siRNA monotherapy and PD-1 siRNA-Doxil (liposomal doxorubicin) combination therapy improved the survival significantly, compared to the control treatment (P < 0.001). Overall, these findings suggest that immunotherapy with siPD-1-loaded liposomes by enhancing T-cell-mediated antitumor immune responses could be considered as a promising strategy for the treatment of melanoma cancer.
Identifiants
pubmed: 34341501
doi: 10.1038/s41417-021-00367-9
pii: 10.1038/s41417-021-00367-9
doi:
Substances chimiques
Liposomes
0
Programmed Cell Death 1 Receptor
0
RNA, Messenger
0
RNA, Small Interfering
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
814-824Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Mullen CA, Schreiber H. Tumor growth and evasion of immune destruction: UV-induced tumors as a model. Surv immunologic Res. 1985;4:264–70.
doi: 10.1007/BF02918734
Sharma P, Shen Y, Wen S, Yamada S, Jungbluth AA, Gnjatic S, et al. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci USA. 2007;104:3967–72.
pubmed: 17360461
pmcid: 1820692
doi: 10.1073/pnas.0611618104
He X, Xu C. PD-1: a driver or passenger of T cell exhaustion? Mol Cell. 2020;77:930–1.
pubmed: 32142689
doi: 10.1016/j.molcel.2020.02.013
Gong J, Chehrazi-Raffle A, Reddi S, Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer. 2018;6:8.
pubmed: 29357948
pmcid: 5778665
doi: 10.1186/s40425-018-0316-z
Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1:405–13.
pubmed: 7882171
doi: 10.1016/1074-7613(94)90071-X
Konstantinidou M, Zarganes-Tzitzikas T, Magiera-Mularz K, Holak TA, Domling A. Immune checkpoint PD-1/PD-L1: is there life beyond antibodies? Angew Chem. 2018;57:4840–8.
doi: 10.1002/anie.201710407
Buchbinder EI, Desai ACTLA-4. and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39:98.
pubmed: 26558876
pmcid: 4892769
doi: 10.1097/COC.0000000000000239
Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubat T, Yagita H, et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996;8:765–72.
pubmed: 8671665
doi: 10.1093/intimm/8.5.765
Bertucci F, Finetti P, Mamessier E, Pantaleo MA, Astolfi A, Ostrowski J, et al. PDL1 expression is an independent prognostic factor in localized GIST. Oncoimmunology. 2015;4:e1002729.
pubmed: 26155391
pmcid: 4485716
doi: 10.1080/2162402X.2014.1002729
Sponaas A-M, Moharrami NN, Feyzi E, Standal T, Rustad EH, Waage A, et al. PDL1 expression on plasma and dendritic cells in myeloma bone marrow suggests benefit of targeted anti PD1-PDL1 therapy. PLoS ONE. 2015;10:e0139867.
pubmed: 26444869
pmcid: 4596870
doi: 10.1371/journal.pone.0139867
Kamphorst AO, Pillai RN, Yang S, Nasti TH, Akondy RS, Wieland A, et al. Proliferation of PD-1 + CD8 T cells in peripheral blood after PD-1–targeted therapy in lung cancer patients. Proc Natl Acad Sci USA. 2017;114:4993–8.
pubmed: 28446615
pmcid: 5441721
doi: 10.1073/pnas.1705327114
Blank C, Mackensen A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother. 2007;56:739–45.
pubmed: 17195077
doi: 10.1007/s00262-006-0272-1
Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, et al. Phase I study of pembrolizumab (MK-3475; anti–PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res. 2015;21:4286–93.
pubmed: 25977344
doi: 10.1158/1078-0432.CCR-14-2607
Falchook GS, Leidner R, Stankevich E, Piening B, Bifulco C, Lowy I, et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer. 2016;4:1–5.
pmcid: 5123387
doi: 10.1186/s40425-016-0176-3
Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004;432:173.
pubmed: 15538359
doi: 10.1038/nature03121
Jagani H, Rao JV, Palanimuthu VR, Hariharapura RC, Gang S. A nanoformulation of siRNA and its role in cancer therapy: in vitro and in vivo evaluation. Cell Mol Biol Lett. 2013;18:120.
pubmed: 23271435
doi: 10.2478/s11658-012-0043-2
Burnett JC, Rossi JJ, Tiemann K. Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol J. 2011;6:1130–46.
pubmed: 21744502
pmcid: 3388104
doi: 10.1002/biot.201100054
Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov. 2009;8:129–38.
pubmed: 19180106
pmcid: 7097568
doi: 10.1038/nrd2742
Dominska M, Dykxhoorn DM. Breaking down the barriers: siRNA delivery and endosome escape. J Cell Sci. 2010;123:1183–9.
pubmed: 20356929
doi: 10.1242/jcs.066399
Ozpolat B, Sood AK, Lopez-Berestein G. Liposomal siRNA nanocarriers for cancer therapy. Adv Drug Deliv Rev. 2014;66:110–6.
pubmed: 24384374
doi: 10.1016/j.addr.2013.12.008
Tsermentseli SK, Kontogiannopoulos KN, Papageorgiou VP, Assimopoulou AN. Comparative study of PEGylated and conventional liposomes as carriers for shikonin. Fluids. 2018;3:36.
doi: 10.3390/fluids3020036
Howard FB, Levin IW. Lipid vesicle aggregation induced by cooling. Int J Mol Sci. 2010;11:754–61.
pubmed: 20386666
pmcid: 2852866
doi: 10.3390/ijms11020754
Jain RK, Stylianopoulos T. Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol. 2010;7:653.
pubmed: 20838415
pmcid: 3065247
doi: 10.1038/nrclinonc.2010.139
Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Tropical J Pharm Res. 2013;12:265–73.
Mirzaaghasi A, Han Y, Ahn S-H, Choi C, Park J-H. Biodistribution and pharmacokinectics of liposomes and exosomes in a mouse model of sepsis. Pharmaceutics 2021;13:427.
pubmed: 33809966
pmcid: 8004782
doi: 10.3390/pharmaceutics13030427
Koning GA, Storm G. Targeted drug delivery systems for the intracellular delivery of macromolecular drugs. Drug Discov Today. 2003;8:482–3.
pubmed: 12818515
doi: 10.1016/S1359-6446(03)02699-0
Metselaar JM, Storm G. Liposomes in the treatment of inflammatory disorders. Expert Opin Drug Deliv. 2005;2:465–76.
pubmed: 16296768
doi: 10.1517/17425247.2.3.465
Faisal SM, Chen J-w, McDonough SP, et al. Y-F. Immunostimulatory and antigen delivery properties of liposomes made up of total polar lipids from non-pathogenic bacteria leads to efficient induction of both innate and adaptive immune responses. Vaccine. 2011;29:2381–91.
pubmed: 21300103
doi: 10.1016/j.vaccine.2011.01.110
Stecher C, Battin C, Leitner J, Zettl M, Grabmeier-Pfistershammer K, Höller C, et al. PD-1 blockade promotes emerging checkpoint inhibitors in enhancing T cell responses to allogeneic dendritic cells. Front Immunol. 2017;8:572.
pubmed: 28588576
pmcid: 5439058
doi: 10.3389/fimmu.2017.00572
Petersen RP, Campa MJ, Sperlazza J, Conlon D, Joshi MB, Harpole DH Jr, et al. Tumor infiltrating Foxp3+ regulatory T‐cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 2006;107:2866–72.
pubmed: 17099880
doi: 10.1002/cncr.22282
Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B, et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007;132:2328–39.
pubmed: 17570208
doi: 10.1053/j.gastro.2007.03.102
Cai J, Wang D, Zhang G, Guo X. The role of PD-1/PD-L1 axis in Treg development and function: implications for cancer immunotherapy. OncoTargets Ther. 2019;12:8437.
doi: 10.2147/OTT.S221340
Wang C, Yi T, Qin L, Maldonado RA, von Andrian UH, Kulkarni S, et al. Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells. J Clin Investig. 2013;123:1677–93.
pubmed: 23478407
pmcid: 3613923
doi: 10.1172/JCI66204
Yoshida K, Okamoto M, Sasaki J, Kuroda C, Ishida H, Ueda K, et al. Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells. BMC Cancer. 2020;20:1–10.
doi: 10.1186/s12885-019-6499-y
Hu J, Sun C, Bernatchez C, Xia X, Hwu P, Dotti G, et al. T-cell homing therapy for reducing regulatory T cells and preserving effector T-cell function in large solid tumors. Clin Cancer Res. 2018;24:2920–34.
pubmed: 29391351
pmcid: 6004229
doi: 10.1158/1078-0432.CCR-17-1365
De La Cruz LM, Nocera NF, Czerniecki BJ. Restoring anti-oncodriver Th1 responses with dendritic cell vaccines in HER2/neu-positive breast cancer: progress and potential. Immunotherapy. 2016;8:1219–32.
doi: 10.2217/imt-2016-0052
Liudahl SM, Coussens L. To help or to harm: dynamic roles of CD4+ T helper cells in solid tumor microenvironments. In Immunology: Immunotoxicology, Immunopathology, and Immunotherapy. Elsevier. 2017;1:97-116. https://doi.org/10.1016/B978-0-12-809819-6.00008-3 .
Nie X, Chen W, Zhu Y, Huang B, Yu W, Wu Z, et al. B7-DC (PD-L2) costimulation of CD4+ T-helper 1 response via RGMb. Cell Mol Immunol. 2018;15:888–97.
pubmed: 28479601
doi: 10.1038/cmi.2017.17
Yamamura M, Modlin RL, Ohmen JD, Moy RL. Local expression of antiinflammatory cytokines in cancer. J Clin Investig. 1993;91:1005–10.
pubmed: 8450029
pmcid: 288053
doi: 10.1172/JCI116256
Oshikawa K, Yanagisawa K, Ohno S, Tominaga S-I, Sugiyama Y. Expression of ST2 in helper T lymphocytes of malignant pleural effusions. Am J Respiratory Crit Care Med. 2002;165:1005–9.
doi: 10.1164/ajrccm.165.7.2105109
Chen Y-M, Yang W-K, Whang-Peng J, Tsai C-M, Perng R-P. An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer. Lung Cancer. 2001;31:25–30.
pubmed: 11162863
doi: 10.1016/S0169-5002(00)00165-3
Chtanova T, Mackay CR. T cell effector subsets: extending the Th1/Th2 paradigm. Adv Immunol. 2001;78:233–66.
Park JY, Jang MJ, Chung YH, Kim KY, Kim SS, Lee WB, et al. Doxorubicin enhances CD4+ T-cell immune responses by inducing expression of CD40 ligand and 4-1BB. Int Immunopharmacol. 2009;9:1530–9.
pubmed: 19778641
doi: 10.1016/j.intimp.2009.09.008
Raskov H, Orhan A, Christensen JP, Gögenur I. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy. Br J Cancer. 2020;124:359–67.
Inozume T, Hanada K-i, Wang QJ, Ahmadzadeh M, Wunderlich JR, Rosenberg SA, et al. Selection of CD8+ PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T-cells. J Immunother. 2010;33:956.
pubmed: 20948441
pmcid: 2980947
doi: 10.1097/CJI.0b013e3181fad2b0
Wedekind MF, Wagner LM, Cripe TP. Immunotherapy for osteosarcoma: where do we go from here? Pediatr Blood Cancer. 2018;65:e27227.
pubmed: 29923370
doi: 10.1002/pbc.27227
Maimela NR, Liu S, Zhang Y. Fates of CD8+ T cells in tumor microenvironment. Computat Struct Biotechnol J. 2019;17:1–13.
doi: 10.1016/j.csbj.2018.11.004
Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298–306.
pubmed: 22419253
doi: 10.1038/nrc3245
Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, et al. PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors. J Clin Investig. 2014;124:2246–59.
pubmed: 24667641
pmcid: 4001555
doi: 10.1172/JCI73639
Li C, Han X. Melanoma cancer immunotherapy using PD-L1 siRNA and imatinib promotes cancer-immunity cycle. Pharm Res. 2020;37:1–10.
doi: 10.1007/s11095-020-02838-4
Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286.
pubmed: 26648870
pmcid: 4664963
doi: 10.3389/fphar.2015.00286
Morris K, Castanotto D, Al-Kadhimi Z, Jensen M, Rossi J, Cooper LJ. Enhancing siRNA effects in T cells for adoptive immunotherapy. Hematology. 2005;10:461–7.
pubmed: 16321811
doi: 10.1080/10245330500233569