Laser‐Activatable In Situ Vaccine Enhances Cancer‐Immunity Cycle

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(52)

Published: Nov. 11, 2023

The immune response in cancer reflects a series of carefully regulated events; however, current tumor immunotherapies typically address single key aspect to enhance anti-tumor immunity. In the present study, nanoplatform (Fe3 O4 @IR820@CpG)-based immunotherapy strategy that targets multiple steps cancer-immunity cycle is developed: 1) promotes release tumor-derived proteins (TDPs), including tumor-associated antigens and pro-immunostimulatory factors), addition direct killing effect, by photothermal (PTT) photodynamic therapy (PDT); 2) captures released TDPs delivers them, together with CpG (a Toll-like receptor 9 agonist) antigen-presenting cells (APCs) promote antigen presentation T cell activation; 3) enhances tumor-killing ability combining anti-programmed death ligand 1 antibody (α-PD-L1), which collectively advances outstanding effects on colorectal, liver breast cancers. broad-spectrum activity Fe3 @IR820@CpG α-PD-L1 demonstrates optimally manipulating anti-cancer immunity not singly but as group provides promising clinical strategies.

Language: Английский

---

In situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(9), P. 4102 - 4117

Published: June 12, 2024

Tumor vaccine, a promising modality of tumor immunotherapy, needs to go through the process antigen generation and loading, drainage lymph nodes (LNs), internalization by dendritic cells (DCs), DC maturation, cross-presentation activate T-cells. However, vaccines are often unable satisfy all steps, leading limitation their application efficacy. Herein, based on smart nanogel system, an

Language: Английский

---

Components, Formulations, Deliveries, and Combinations of Tumor Vaccines

ACS Nano, Journal Year: 2024, Volume and Issue: 18(29), P. 18801 - 18833

Published: July 9, 2024

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating restoring the body's own immune system. Currently, various formulations vaccines have been developed, including cell membrane DNA mRNA polypeptide virus-vectored and tumor-in-situ vaccines. There are also multiple delivery systems for such as liposomes, vesicles, viruses, exosomes, emulsions. In addition, to decrease risk escape tolerance that may exist with a single vaccine, combination therapy radiotherapy, chemotherapy, checkpoint inhibitors, cytokines, CAR-T therapy, photoimmunotherapy is effective strategy. Given critical role in here, we look back history discuss antigens, adjuvants, formulations, systems, mechanisms, future directions

Language: Английский

---

Engineering platforms for localized long-acting immune modulation

Journal of Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 153(3), P. 572 - 575

Published: Jan. 20, 2024

Systemic immunotherapeutics have been a clinical staple in the treatment of cancer, infectious diseases, organ and cell transplantation, autoimmunity, allergies. Although their utility remains unquestioned, systemic administration these drugs is associated with limited efficacy, significant adverse off-target effects, transient activity, requirement for frequent repeated dosing. To this end, recent technological advancements provided novel means sustained drug delivery to specific tissues targeted localized approaches immunotherapeutics. In article, we present various cutting-edge platform technologies, including implants, multireservoir systems, scaffolds encapsulating immunomodulatory agents local administration. Examples application allergy, diseases are discussed, highlighting potential such systems innovative intervention. Immunomodulatory therapies engage immune-relevant targets manage or treat variety diseases. Depending on disease, can be conventional small molecule pharmaceutics biologic agents, nucleic acids, proteins, cells.1Campa-Carranza J.N. Paez-Mayorga J. Chua C.Y.X. Nichols J.E. Grattoni A. Emerging strategies circumvent immunosuppression transplantation.Expert Opin Drug Del. 2022; 19: 595-610Crossref PubMed Scopus (7) Google Scholar demonstrated efficacy applications as transplantation allergic However, unfavorable physiologic kinetics subsequent therapeutic pose challenges. causes dispersion, whereas hinges presence high concentrations activity within target at disease site.2Kichloo Albosta M. Dahiya D. Guidi J.C. Aljadah Singh et al.Systemic effects toxicities immunotherapy: review.World J Clin Oncol. 2021; 12: 150-163Crossref Because low levels, typically required but not always feasible. Further, serious reactions on-target side owing overactivation oversuppression immune system impediments successful management. Additionally, attributable nonspecificity further exacerbate safety concerns. innovations that provide approach longer duration management poised new frontier therapies. Long-acting could reduce dosage, frequency, toxicities, which turn improves medication adherence, yielding long-lasting preventative curative effect. Of relevance, long-acting disease-targeting platforms clinically established chronic conditions HIV,3Pons-Faudoa F.P. Di Trani N. Capuani S. Campa-Carranza Nehete B. Sharma al.Long-acting refillable nanofluidic implant confers protection against SHIV infection nonhuman primates.Science Translational Medicine. 2023; 15eadg2887Crossref (6) diabetes, psychiatric illnesses.4Baryakova T.H. Pogostin B.H. Langer R. McHugh K.J. Overcoming barriers patient adherence: case developing systems.Nature Reviews Discovery. 22: 387-409Crossref (34) Considering success approaches, highlight few technologies developed immunomodulation achieve control particular focus (Fig 1). Immunotherapy has transformed cancer an unprecedented manner. inherent acquired heterogeneity leads variable responses. Immune evasion leading contributor failure. Thus, educate identify foreign, nonself allows eluding evasion. Pertinent this, context situ vaccines,5Liu H.-C. Davila Gonzalez Viswanath D.I. Vander Pol R.S. Saunders S.Z. al.Sustained intratumoral agonist CD40 antibody overcomes immunosuppressive tumor microenvironment pancreatic cancer.Adv Sci. 102370054Google Scholar,6Yousefpour P. Ni K. Irvine D.J. Targeted modulation cells using engineered biomaterials.Nat Rev Bioeng. 1: 107-124Crossref sphere applicability broad extends vaccines These rely biodegradable situ–forming hydrogels, polymers, nanoformulations capable immunomodulators antigens. preclinical setting, some highly efficacious models settings hold much promise translation.7Ou B.S. Saouaf O.M. Baillet Appel E.A. Sustained improving adaptive responses.Adv Deliver Rev. 187114401Crossref (30) ultimate multiple factors, practicality acceptability among others. note, may require booster administration, unfeasible limit relevance technology. addressing need long-term drug8Liu Pesaresi F. Xu Y. Zhang L. al.Potentiating antitumor through radiation anti-CD40 anti-PDL1.Int Radiat Oncol Biol Phys. 110: 492-506Abstract Full Text PDF (33) antigen developed. Among them, NanoLymph was designed homing and/or reprogramming targets.9Viswanath Liu H.C. Huston D.P. biomaterial-based personalized vaccines.Biomaterials. 280121297Crossref (26) The 3-dimensional (3D) printable subcutaneous deployment dual reservoirs, each immunomodulator elution presentation. scale (∼8 mm diameter 2 thickness) "D-shaped" agnostic offers flexibility use wide spectrum When reservoirs loaded GM-CSF resiquimod (a Toll-like receptor 7/8 agonist) well peptide antigen, dendritic (DCs) recruited site activated antigen-presenting (APCs). Thereafter, DCs migrate lymph nodes initiate antigen-specific T-cell response. versatility immunomodulators, antigens, will permit orchestration cell–mediated response across range acting prophylactic vaccine clear antigens adopted generate immunity pathogens. autologous whole lysates used source, facilitating generation directed toward unique antigenic repertoire patient's own tumor.10Diao Rethinking source: based cell/tissue lysate cell.Adv 102300121Crossref (13) crucial generating potent activation. context, peritumoral implantation more effective than distal site, although placement would compromise accessibility adjuvant loading refilling. refillability aspect technology advantageous treatment. Other platforms, nanoparticle microencapsulation, gradually release components (antigens adjuvants) pathogens, ensuring immunization.11Kerr M.D. Johnson W.T. McBride D.A. Chumber A.K. Shah N.J. Biodegradable enhancing delivery.Bioeng Transl Med. 8e10591Crossref (1) Scholar,12Roth G.A. Picece V.C.T.M. Ou Luo W. Pulendran Designing spatial temporal responses.Nat Mater. 7: 174-195Crossref (114) Compared traditional vaccines, shown enhanced fewer doses, makes them particularly relevant resource-limited areas. challenges include stability viability components, precise rates, extensive testing development. An alternative form immunomodulation, adoptive therapy, engineers T ex vivo vivo. after reinfusion, only fraction actually reach tumor, where they encounter difficulty penetrating mass.13Zhang A.Q. Hostetler Chen L.E. Mukkamala V. Abraham Padilla L.T. al.Universal redirection CAR solid tumours via membrane-inserted ligands CAR.Nat Biomed Eng. 1113-1128Crossref (9) More importantly, surface increases it proliferates, resulting short-lived responses therapy. address challenges, biomaterials–based platform, termed synergistic vaccination depot (SIVET), developed.14Adu-Berchie Brockman J.M. T.W. D.K.Y. Najibi A.J. al.Adoptive transfer host recruitment cryogel promotes tumors.Nat Commun. 14: 3546Crossref SIVET advances beyond previous work centered solely DCs. Composed alginate-collagen hybrid cryogel, controlled adoptively transferred immunostimulants attract APCs. facilitates debulking, dying serve source. Simultaneous FMS-like tyrosine kinase 3 ligand (FLT3L) CpG stimulates continual APC activation, respectively. This enables escape representing intervention immunomodulation. Transplant patients viable allografts restore dysfunctional organs tissues. both transplantation. rejection barrier widespread adoption. Graft results destruction transplanted tissues, triggered by even slight mismatches HLA alleles. As such, regimens commonly avoid rejection. Unfortunately, severe increased risks infections, neoplasms, damage. challenge, numerous modulation, sparing body from deleterious effect lifelong suppression.15Chua Jiang A.Y. Eufrásio-da-Silva T. Dolatshahi-Pirouz Orive G. al.Emerging therapeutics.Trends Biotechnol. 41: 358-373Abstract (8) minimizing immunogenicity clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated protein 9 (Cas9) genome editing; leveraging RNA therapeutics cytokine induce tolerance; cotransplantation reg cells, Sertoli mesenchymal stem cells; agents.15Chua share suitable ideal achieves retention while providing tissue microenvironment. One NICHE, dual-reservoir 3D-printed nylon subdermal islets type 1 diabetes (T1D). native microenvironment, densely vascularized intraislet capillaries, obtain approximately 20% blood supply. Following implantation, NICHE relies angiogenic properties dense vessel network supplying oxygen, nutrients, rapid glucose insulin exchange function islets.16Paez-Mayorga Farina Lotito M.L. Niles J.A. Salazar H.F. al.Enhanced vascularization encapsulation device platelet-rich plasma cells.Adv Healthc 2020; 9e2000670PubMed prevented immunosuppressants thymoglobulin, cytotoxic lymphocyte–associated antigen-4 (CTLA-4) immunoglobulin, anti-CD40-L, depleting impeding activation costimulatory pathway Notably, transcutaneous reloading reservoir, extending functionality over long term. different (eg, growth immunoadjuvants, cytokines) alone combination, simultaneous sequential support during phases engraftment remodeling. allogenic islet model, immunocompetent diabetic rats, achieved T1D reversal no sign throughout 180 days analysis.17Paez-Mayorga Hernandez al.Implantable niche allotransplantation rats.Nature Communications. 13: 7951Crossref (11) Local also codelivery adjuvant–releasing microparticles gels cells.18Wang X. Brown N.K. Wang Shariati Fuchs al.Local prevent allo-rejection insulin-producing cells.Advanced Science. 82003708Google notable example, FasL-modified microgels conferred co.transplanted non.human primates. Here, Fas receptor/Fas (FasL) leveraged confer privilege tolerance self-antigens inducing apoptosis infiltrating lymphocytes inflammatory cells.19Lei Coronel M.M. Yolcu E.S. Deng H. Grimany-Nuno O. Hunckler al.FasL acceptance primates.Sci Adv. 8eabm9881Crossref (29) translatable T1D, neurodegenerative cardiovascular pathologies hormone deficiencies. Their adaptability dosing timing duration, ability localize distribution render development therapeutics. given multicomponent nature, regulatory approval complex translational efforts. Allergic disorders affect one-third population remain challenge. allergen avoidance method prevention, possible, symptomatic medications adequate. Over past century, immunotherapy (AIT) evolved IgE-mediated hypersensitivity disorders.20Durham S.R. Shamji M.H. Allergen past, future.Nat Immunol. 23: 317-328Crossref (75) AIT strategy many aeroallergens stinging insect allergens injection extracts, recently, recombinant allergens, chemically altered (allergoids), cell-targeted peptides. Sublingual aeroallergens, oral approved peanut allergy desensitization. Epicutaneous, microneedle patch, mRNA vaccine, intralymphatic under investigation, growing number additional improve exploratory. combining immunomodulating agonists, mAbs cytokines, receptors. goal tolerance.20Durham Mechanistically, AIT-induced manifested induction DCs, B produce IL-10 TGF-β inhibiting TH2 innate lymphoid hence reducing cytokines IgG-blocking antibodies inhibit binding IgE allergen. Efforts enhance tolerance-inducing exploring nanoparticles, patches,21Paris J.L. Vora L.K. Torres M.J. Mayorga C. Donnelly R.F. Microneedle array patches allergen-specific immunotherapy.Drug Discov Today. 28103556Crossref (4) programmable implants agents. Nanoparticle formulations optimized physical chemical size, pH, loading, optimal cellular targeting uptake.22Johnson Duschl Himly Nanotechnology-based potentials adjuvants research.Vaccines (Basel). 8: 237Crossref (28) Importantly, offer topical, oral, Murine studies allergen-loaded nanoparticles tolerance.23Hughes K.R. M.N. Landers J.J. Janczak K.W. Turkistani Rad L.M. al.Masked safely attenuates anaphylactic murine allergy.Front Allergy. 3829605Crossref potentially passive epicutaneous APCs skin, thereby AIT. tolerance.24Landers Shakya Zarnitsyn Patel Baker Jr., J.R. al.Targeted skin desensitization peanut.Immunotherapy. 539-552Crossref (16) There implantable microchambers, aforementioned 3D printed applications,3Pons-Faudoa exploited Such entail NanoLymph, chamber promote migration differentiation tolerance. Overall, convergence engineering interdisciplinary collaborations likely yield treating near future. conclusion, antigen-delivery broadened management, tunable extend simplifying regimen quality life. evident field immunotherapy, long-lasting, transformative impact care. cost-effectiveness medical treatments contribute health care equity. Enhanced reduced lower frequency direct costs decrease expenses, those related

Language: Английский

---

Recent advances in mRNA‐based vaccine for cancer therapy; bench to bedside

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(2)

Published: Feb. 25, 2024

The messenger RNA (mRNA) vaccines have progressed from a theoretical concept to clinical reality over the last few decades. Compared conventional vaccination methods, these number of benefits, such as substantial potency, rapid growth, inexpensive production, and safe administration. Nevertheless, their usefulness was restricted up now due worries about erratic ineffective circulation mRNA in vivo. Thankfully, largely been allayed by recent technological developments, which led creation multiple platforms for cancer viral infections. demonstrated powerful alternative traditional because high safety efficacy, capacity development, potential rapid, low-cost manufacturing. paper will examine present status vaccine technology suggest future paths advancement application this exciting platform common therapeutic choice.

Language: Английский

---

Macrophage lysate-derived cytokine network combined with silk fibroin hydrogel promotes diabetic vascularized bone regeneration

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 490, P. 151892 - 151892

Published: May 3, 2024

Cell-based therapies are used extensively in tissue engineering because of their great biosafety and diverse biological functions. Among them, macrophage lysate provides a comprehensive rich network cytokines to modulate the local immune microenvironment. However, effective strategies for lysate-based biomaterials with immune-regulatory function still lacking. In this study, we engineered silk fibroin hydrogel loaded THP-1 whole-cell regulate microenvironment promote vascularized bone regeneration diabetic defects. Specifically, by modulating expression pattern key enzyme energy metabolism (mitochondrial phosphoenolpyruvate carboxykinase, PCK2) cells, generated enriched anti-inflammatory factors. This facilitated osteogenic differentiation BMSCs angiogenesis HUVECs vitro, incorporating immunomodulatory into enhanced diabetes. Mechanistically, revealed that PCK2 activated nuclear factor-kappa B (NF-κB) signaling pathway macrophages using proteomic profiling. research new insights design cell-derived biomaterials, aiming improve therapeutic outcomes pathological

Language: Английский

---

Cancer biotherapy: review and prospect

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 27, 2024

Abstract Malignant tumors pose a grave threat to the quality of human life. The prevalence malignant in China is steadily rising. Presently, clinical interventions encompass surgery, radiotherapy, and pharmaceutical therapy isolation or combination. Nonetheless, these modalities fail completely eradicate tumor cells, frequently leading metastasis recurrence. Conversely, biotherapy has emerged as an encouraging fourth approach preventing managing owing its safety, efficacy, minimal adverse effects. Currently, range techniques are employed, including gene therapy, vaccines, monoclonal antibody cancer stem cell cytokine adoptive cellular immunotherapy. This study aims comprehensively review latest developments biological treatments for tumors.

Language: Английский

---

The anti-tumor effect of the IFNγ/Fas chimera expressed on CT26 tumor cells

Animal Cells and Systems, Journal Year: 2025, Volume and Issue: 29(1), P. 46 - 56

Published: Jan. 2, 2025

Interferon gamma (IFNγ) is well-known for its ability to stimulate immune cells in response pathogen infections and cancer. To develop an effective cancer therapeutic vaccine, CT26 colon carcinoma were genetically modified express IFNγ either as a secreted form (sIFNγ) or membrane-bound form. For the expression, was fused with Fas (mbIFNγ/Fas), incorporating extracellular cysteine-rich domains, transmembrane, cytoplasmic domains of Fas. The tumor expressing sIFNγ mbIFNγ/Fas showed slower growth rates compared mock-transfected cells. Furthermore, tumorigenicity significantly lower than that mock control. Remarkably, about 85% mice injected mbIFNγ/Fas-expressing tumors remained tumor-free over two months. Mice rejected developed systemic anti-tumor immunity against cells, which characterized by enhanced levels CD4+ CD8+ T well natural killer (NK) Interestingly, splenocytes activated exhibited higher cytotoxicity those sIFNγ. These findings suggest chimera could be promising strategy developing whole cell vaccines gene therapies immunotherapy.

Language: Английский

---

Whole‐Component Antigen Nanovaccines Combined With aTIGIT for Enhanced Innate and Adaptive Anti‐tumor Immunity

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Using entire tumor cells or tissues that display both common and patient‐specific antigens can potentially trigger a comprehensive long‐lasting anti‐tumor immune response. However, the limited immunogenicity, low uptake efficiency, susceptibility to degradation of whole‐component present significant challenges. In this study, we employed lysates (TLs) as antigens, in conjunction with MgAl‐layered double hydroxide (MA) nanoadjuvants Mn 2+ immunostimulants, create personalized MMAT (Mn ‐MA‐TLs) nanovaccines. After subcutaneous injection nanovaccines, high local concentrations TLs facilitated recruitment activation antigen‐presenting (APCs), thereby inducing robust adaptive Remarkably, nanovaccines enabled lysosomal escape, enhanced antigen cross‐presentation, activated cyclic GMP‐AMP synthase (cGAS)‐stimulator interferon genes (STING) pathway APCs. Furthermore, when combined anti‐TIGIT monoclonal antibody (aTIGIT), an checkpoint inhibitor, not only stimulated T‐cell‐based responses but also NK‐cell‐based innate immunity, effectively suppressing growth, recurrence, metastasis. Thus, ternary developed here introduced pioneered paradigm for rapid preparation immunostimulants into offering new prospects clinical immunotherapies.

Language: Английский

---

A facile approach to preparing personalized cancer vaccines using iron-based metal organic framework

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Background Considering the diversity of tumors, it is great significance to develop a simple, effective, and low-cost method prepare personalized cancer vaccines. Methods In this study, facile one-pot synthetic route was developed vaccines using model antigen or autologous tumor antigens based on coordination interaction between Fe 3+ ions endogenous fumarate ligands. Results Herein, Fe-based metal organic framework can effectively encapsulate with high loading efficiency more than 80%, act as both delivery system adjuvants for antigens. By adjusting synthesis parameters, obtained are easily tailored from microscale rod-like morphology lengths about 0.8 μm (OVA-ML) nanoscale sizes 50~80 nm (OVA-MS). When cocultured antigen-presenting cells, enhance uptake Th1 cytokine secretion ones. Nanoscale (OVA-MS, dLLC-MS) lymph node targeting cross-presentation antigens, mount antitumor immunity, inhibit growth established in tumor-bearing mice, compared (OVA-ML, dLLC-ML) free Conclusions Our work paves ways facile, rapid, preparation approach

Language: Английский

---