Nanoimmunotherapy: application of nanotechnology for sustained and targeted delivery of antigens to dendritic cells
2011; Future Medicine; Volume: 7; Issue: 1 Linguagem: Inglês
10.2217/nnm.11.171
ISSN1748-6963
AutoresZhiping Zhang, Yajun Guo, Si‐Shen Feng,
Tópico(s)Monoclonal and Polyclonal Antibodies Research
ResumoNanomedicineVol. 7, No. 1 EditorialFree AccessNanoimmunotherapy: application of nanotechnology for sustained and targeted delivery of antigens to dendritic cellsZhiping Zhang, Yajun Guo & Si-Shen FengZhiping ZhangTongji School of Pharmacy, Huazhong University of Science & Technology, Wuhan 430030, China, Yajun GuoInternational Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China & Si-Shen Feng* Author for correspondenceDepartment of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore. Published Online:22 Dec 2011https://doi.org/10.2217/nnm.11.171AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: antigen deliverycancer nanotechnologydendritic cellsimmune responsenanobiotechnologynanocarriersCancer is one of the most troublesome diseases as it is difficult to treat, let alone thoroughly cure. This is because cancer suppresses the body's immune system and, thus, can spread so quickly that any treatment is inefficient. Immunotherapy is developed as a medical treatment of disease by inducing, enhancing or suppressing an immune response; however, it has not been as satisfactory due to the lack of knowledge on the cellular and molecular basis of the immune reaction. Cancer immunotherapy is mainly focused on manipulating the patient's own immune system to recognize and destroy cancer cells. It can induce specific killing of tumor cells to evade therapeutic effect on normal cells, target primary and secondary metastases by stimulating antitumor immune response, and realize possible long-term protection from future recurrences by immunological memory function. Dendritic cells (DCs) are important antigen-presenting cells (APCs) for generating tumor-specific cytotoxic T lymphocytes (CTLs). DCs can migrate antigens to regional lymph nodes and finally effectively prime naive T-cell response. Therefore, targeted delivery of antigens to DCs to induce strong CTL response is the most preferable vaccine strategy. Antigens can be delivered in variable formulations, such as proteins, peptides, tumor lysates or complementary DNA encoding tumor antigens, and so on. The most widely used immunotherapeutic approach uses the ex vivo DC-based cancer vaccines, which remains insufficient in clinical patients (limited to <7% only). It requires cell isolation, culture and pulsation with DC, DC modifications, and DC migration to the lymph nodes and subsequent activation of the cognate T cells. The whole process is labor/laboratory sensitive, expensive, tedious, less reproducible, and nonefficient in inducing T-cell response. There are very limited alive cells (<10%) and few cells migrating to lymph nodes (0.5–2.0%) after transplantation, and thus limited efficacy [1].To efficiently induce antitumor CTL responses through vaccinations, a sufficient amount of antigen needs to be presented for a sufficient period of time by licensed DCs that are activated by adjuvants through alarm or danger signals. The aim of nanoimmunotherapy is to apply and further develop nanotechnology to solve the problems encountered in immunotherapy, and is mainly focused on development of various nanocarriers for sustained, controlled and targeted delivery of antigens to DCs. Nanocarriers may include polymer conjugations, micelles, liposome, solid lipid nanoparticles and nanoparticles of biodegradable polymers. In this regard, nanotechnology-based delivery of antigens may be one of the promising strategies for cancer immunotherapy due to its dose-sparing and prolonged antigen-presentation features. This kind of delivery system can also provide a sustainable supply of sufficient antigens and adjuvants. Furthermore, much stronger T-cell responses can be elicited. Encapsulation of antigens in nanocarriers has been reported to directly deliver incorporated antigens to APCs and to confer their sustained release by avoiding proteolytic degradation and improving their stability. Nanocarriers can also realize targetable, controllable and selective uptake of antigens by DCs without causing excessive inflammatory responses, which is often the case with other vaccine formulations with currently available adjuvants, such as Freund's adjuvant or aluminum salts. In addition, compared with soluble proteins or peptides uptaken by APCs via macropinocytosis and poorly presented as MHC ligands on the cell surface in vivo, the antigens encapsulated in nanocarriers are internalized via phagocytosis and can thus be more efficiently crosspresented on MHC class I molecules [2].Targeting pathogen recognition receptors: single antigen & adjuvant-loaded nanoparticles induced T-cell responseTumor-associated antigens are normally poor immunogens and can not induce strong T-cell immune responses without appropriate adjuvants and/or improved delivery systems. Liposomes or other nanoparticles may function as adjuvants but lack intrinsic immunostimulatory effects and thus codelivery of immune potentiators is essential to induce robust T-cell immunity. Immune potentiators include: acting as a 'danger-signal'; pathogen recognition receptors (signal 0); and costimulatory molecules for activating naive T cells (signal 2) [3]. Toll-like receptors (TLRs) are the most extensively studied subclass of pattern recognition receptors, including lipopolysaccharides, peptidoglycans, lipoproteins, flagellin and unmethylated CpG motifs. Codelivery of antigen and TLR ligand has potency to steer the immune bias, but it depends on the ligand [4]. Nanoscopic vaccine delivery systems can protect TLR ligands against degradation, provide sustained and efficient delivery to DCs, and reduce toxic effects from repeated systemic administration. Antigens and maturation stimuli must be coentrapped in the same nanocarriers to deliver the components to the same phagosomes inside the DCs for subsequent eliciting optimized immune responses. If DCs take up antigens first it may lead to tolerance, while if TLRs stimulate DCs first maturated DCs can not realize efficient antigen presentation [5]. We have recently demonstrated that poly(lactic-co-glycolic acid) nanoparticles carrying peptide antigens could be efficiently uptaken by DCs and induce strong antigen-specific T-cell responses in vitro and in vivo. Furthermore, vaccination of poly(lactic-co-glycolic acid)-nanoparticles can enhance T-cell response and 1000-fold lower antigen concentration for similar levels of cytokine secretion compared with a soluble formulation [6].Targeting C-type-lectin receptor delivery of antigen-loaded nanocarriersC-type-lectin receptors are classified into type I (e.g., mannose receptor and DEC-205) and type II (e.g., DC-SIGN, MGL and Langerin). Targeting DC antigen delivery can enhance the DC function and subsequent T-cell responses, and thus precise engineering on the number, type and density of targeting ligands were developed. Cruz et al. has demonstrated that DC-SIGN targeting poly(lactic-co-glycolic acid) nanoparticles can improve antigen presentation by human DCs and similar levels of T-cell response under 10–100-fold lower concentrations of antigen, compared with the nontargeted formulations [7].Lipid-enveloped poly(lactic-co-glycolic acid) nanoparticles carrying multiple antigenic epitopes & TLRs for efficient induction of antitumor immunityAlthough delivery of antigens by nanoparticles has demonstrated protective immunity in a mouse model, complete tumor rejection could not be achieved in experiment. This may be attributed to selection pressure by the immune system, which induced the loss of antigen presentation in vivo[6]. It should be noted that tumor cells could develop multiple mechanisms to escape from antitumor immunity, including: ▪ Downregulation of antigens at their surface that makes them invisible to CTLs;▪ Secretion of proteins from tumors that can inhibit effector T-cell responses and promote the production of regulatory T cells to suppress immune response;▪ Development of lymphoid tissue-like stromal structures to mimic the functionality of secondary or tertiary lymphoid tissue and result in tumor immune tolerance and suppression [8].We isolated tumor cells and stained cells for H-2Kb/Db expression or by MS-immunoprecipitation analysis. The loss of almost all the antigens from tumor cells has been exhibited. It was also evidenced by a similar experiment performed by the Fréchet group using ELISA and PCR analysis. A single epitope restricted to a particular MHC type might be insufficient for inducing appropriate antitumor immune responses. As Fréchet suggested, incorporation of multiple natural cancer antigens in the same carrier can make tumor cells more difficult to evade from the immune system [9]. Therefore, simultaneous immunization with multiple antigens would be advantageous for making tumor cells more difficult to escape from the surveillance of the immune system by evoking immune responses specific to multiple MHC-restricted T-cell antigens. Nanoparticles carrying multiepitope peptides were developed as a nanoparticle cocktail, which carries multipeptide by mixing different single peptide and monophosphoryl lipid A (MPLA, TLR4)-loaded nanoparticles (data to be published). Both nanoparticles carrying either a single peptide or peptide cocktail could clearly induce T-cell responses specific to the vaccinated peptides in the draining lymph nodes and spleen separated from the vaccinated mice. However, nanoparticles loaded with multiple peptides induced significantly weaker antigen-specific T-cell responses than those carrying a single peptide. Nanoparticle cocktail enhanced suppression of tumor growth in mice and was more effective for controlling tumor growth than those containing a single peptide. In particular, the inhibitory effect of nanoparticles containing three peptides was strongest, suggesting that each peptide had synergistic effects. In addition, mice immunized with nanoparticles containing three peptides showed significantly longer overall survival than those immunized with phosphate buffer saline or single peptide-loaded nanoparticles.Nanoparticle combinations of CTL epitope & T-helper epitope with effective adjuvant in targeting C-type-lectin receptors and TLRs can be effective vectors for vaccination against tumorMimicking and amplifying the physiological immune response can induce an efficient cytotoxic response. DC maturation depends on the signals provided by innate and adaptive immunity. CD4+ T-helper (Th) lymphocytes primed after recognition of specific Th eptiopes can provide adaptive immunity. Innate immunity is provided by pathogens or damaged cells, provided by TLRs or even the particulate carrier itself. Thomann et al. developed liposomes against ErbB2 protein-expressing tumor cells containing ErbB2 p63–71 CTL peptide and HA307–319 Th epitopes, and synthetic agonist, TLR2/1 or TLR2/6, by individually conjugating them to the surface of the same liposomes to realize codelivery of antigens and danger signals for DC maturation and migration. Mannosylated ligands were also incorporated into this construction to increase APC targeting. Combinational peptide- and agonist-loaded liposomes with targeting ligand demonstrated more effective vaccine construction against tumor. Adjuvant quantity can be reduced more than 100-fold lower after inducing targeting ligand in liposomes without affecting its efficiency in vaccination. It seems that incorporating eptiopes and adjuvant in the same particular carrier is essential to realize the same targeting cells. Furthermore, the immune response elicited from immunization of ErB2-related targeted liposome can also destroy the ErB2-negative tumor cells. A humoral epitope spreading in cancer patients after immunization with an ErB2 epitope-based vaccine has also been presented in the clinic. There is an epitope spreading after activation of the T-cell response from specific tumor-associated antigens [10]. It seems that combination of multi-MHC class I and Th epitopes, targeting TLR agonists and C-type-lectin receptor ligands in single particles, may be more efficient to induce T-cell response. Nanovesicles can easily realize this combinational codelivery of multiple TLR and/or C-type-lectin receptor ligands in the same vaccine formulation, and promotes stronger T-cell response and resistance to T regulatory cell-mediated immune suppression [11]. However, to enhance antitumor effects in the vaccine study, the precise mechanism, by which T-cell responses were inhibited, remains to be clarified. In addition, more issues, including the vaccination protocol, such as dose, timing and route of administration, physicochemical property of the nanocarriers and selection/combination of antigens, adjuvants or more, would also need empirical development to more effectively prevent tumor escape mechanisms for future clinical application.Administration route & psychochemical property effectThe nanoparticle uptake and T-cell response may depend on the particles size and also the immunization route. Feng et al. have studied the particle size effect on cellular uptake of the nanoparticles for chemotherapy and found that nanoparticles with a diameter of 100–200 nm may have best effects [7,12,13]. Carstensa et al. also demonstrated that larger particles showed deposition and strongest retention at the site of injection. Whereas, antigen-loaded smaller particles exhibited an increase of antigen-specific, functional CD8+ T-cells and higher antibody levels compared with antigen-loaded larger particles or naked antigen [14]. The administration route may also be of special interest for nanoparticle vaccine delivery systems as nanoparticles can be naturally phagocytosed by various APCs or be engineered for targeting specific tissues or cells. Mohanan et al. demonstrated that IgG2a associated with Th1-type response strongly depends on the vaccine route, ranked as intralymphatic, intradermal (intramuscular), subcutaneous route, whereas the IgG1 response associated with Th2-type immune responses is not sensitive to the vaccine route [15].Combined immunotherapy with other therapies, such as chemotherapyCombined immunotherapy with other therapies such as chemotherapy may promote synergistic effects for more efficient cancer therapy. Recently, Herber et al. demonstrated a new therapeutic strategy, immunochemotherapy, by combining specific drugs and vaccination protocols in a strategy. This strategy can reverse tumor-induced immunosuppression during therapeutic vaccination and conventional chemotherapy, and realize a synergistic effect [16]. In addition, needle-free vaccination may be a more promising strategy for eliciting antigen-specific humoral and cellular immune responses, as demonstrated by using cholesteryl-group-bearing pullulan nanogel for intranasal administration [17] or nanolayered microneedles for transcutaneous delivery [18].Financial & competing interests disclosureThis work is supported by the 7th Singapore–China Cooperative Research Project Call between Agency of Science, Technology and Research (A*STAR), Singapore (SERC Grant # 102–145–0118), and The Ministry of Science and Technology (MOST), China; and the Innovation Fund of HUST (2010QN030) and the Important National Science & Technology Specific Projects, China (2012CB932500). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.References1 Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat. Med.10,909–915 (2004).Crossref, Medline, CAS, Google Scholar2 Krishnamachari Y, Geary SM, Lemke CD, Salem AK. Nanoparticle delivery systems in cancer vaccines. Pharm. Res.28,215–236 (2011).Crossref, Medline, CAS, Google Scholar3 Hamdy S, Haddadi A, Ghotbi Z, Hung RW, Lavasanifar A. Part I: targeted particles for cancer immunotherapy. Curr. Drug Deliv.8,261–273 (2011).Crossref, Medline, CAS, Google Scholar4 Bal SM, Hortensius S, Ding Z, Jiskoot W, Bouwstra JA. Co-encapsulation of antigen and Toll-like receptor ligand in cationic liposomes affects the quality of the immune response in mice after intradermal vaccination. Vaccine29,1045–1052 (2011).Crossref, Medline, CAS, Google Scholar5 Kazzaz J, Singh M, Ugozzoli M, Chesko J, Soenawan E, O'Hagan DT. Encapsulation of the immune potentiators MPL and RC529 in PLG microparticles enhances their potency. J. Control. Release110,566–573 (2006).Crossref, Medline, CAS, Google Scholar6 Zhang ZP, Tongchusak S, Mizukami Y et al. Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery. Biomaterials32,3666–3678 (2011).Crossref, Medline, CAS, Google Scholar7 Cruz LJ, Tacken PJ, Fokkink R et al. Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro. J. Control. Release144,118–126 (2010).Crossref, Medline, CAS, Google Scholar8 Zindl CL, Chaplin DD. Tumor immune evasion. Science328,697–698 (2010).Crossref, Medline, CAS, Google Scholar9 Beaudette TT, Bachelder EM, Cohen JA et al. In vivo studies on the effect of co-encapsulation of CpG DNA and antigen in acid-degradable microparticle vaccines. Mol. Pharm.6,1160–1169 (2010).Crossref, Google Scholar10 Thomann JS, Heurtault B, Weidner S et al. Antitumor activity of liposomal ErbB2/HER2 epitope peptide-based vaccine constructs incorporating TLR agonists and mannose receptor targeting. Biomaterials32,4574–4583 (2011).Crossref, Medline, CAS, Google Scholar11 Mottram PL, Leong D, Crimeen-Irwin B et al. Type 1 and 2 immunity following vaccination is influenced by nanoparticle size: formulation of a model vaccine for respiratory syncytial virus. Mol. Pharm.4,73–84 (2007).Crossref, Medline, CAS, Google Scholar12 Win KY, Feng SS. Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials26,2713–2722 (2005).Crossref, Medline, CAS, Google Scholar13 Kulkarni SA, Feng SS. Surface functionalized nanoparticles of biodegradable polymers for targeted delivery of diagnostic and therapeutic agents across the blood–brain barrier (BBB). Nanomedicine (Lond.)6(2),377–394 (2011).Link, CAS, Google Scholar14 Carstensa MG, Camps MGM, Henriksen-Lacey M et al. Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines. Vaccine29(29–30),4761–4770 (2011).Crossref, Medline, Google Scholar15 Mohanan D, Slütter B, Henriksen-Lacey M et al.Administration routes affect the quality of immune responses: a cross-sectional evaluation of particulate antigen-delivery systems. J. Control. Release147,342–349 (2010).Crossref, Medline, CAS, Google Scholar16 Herber DL, Cao W, Nefedova Y et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nat. Med.16,880–886 (2010).Crossref, Medline, CAS, Google Scholar17 Nochi T, Yuki Y, Takahashi H et al. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines. Nat. Mater.9,572–578 (2010).Crossref, Medline, CAS, Google Scholar18 DeMuth PC, Su Xf, Samuel RE , Hammond PT , Irvine DJ. Nano-layered microneedles for transcutaneous delivery of polymer nanoparticles and plasmid DNA. Adv. Mater.22,4851–4856 (2010).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByPolymeric hydrogel as a vitreous substitute: current research, challenges, and future directions11 June 2021 | Biomedical Materials, Vol. 16, No. 4Heparanase-induced proliferation and inhibition of apoptosis are associated with the phosphatase and tensin homologue deleted on chromosome 10/focal adhesion kinase signaling pathway in multiple myelomaMaterials Express, Vol. 11, No. 5Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport12 October 2020 | Current Eye Research, Vol. 46, No. 4Fish mucus stabilized iron oxide nanoparticles: fabrication, DNA damage and bactericidal activity30 July 2020 | Inorganic and Nano-Metal Chemistry, Vol. 51, No. 4Foldable capsular vitreous body implantation for treatment of traumatic retinal detachment: two case reports9 February 2021 | Journal of International Medical Research, Vol. 49, No. 2A 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the 7th Singapore–China Cooperative Research Project Call between Agency of Science, Technology and Research (A*STAR), Singapore (SERC Grant # 102–145–0118), and The Ministry of Science and Technology (MOST), China; and the Innovation Fund of HUST (2010QN030) and the Important National Science & Technology Specific Projects, China (2012CB932500). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download
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