bims-engexo 2024-07-07 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2024‒07‒07
thirteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Exosome for mRNA delivery: strategies and therapeutic applications.
Empowering Exosomes with Aptamers for Precision Theranostics.
From bench to bedside: The promising value of exosomes in precision medicine for CNS tumors.
Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.
Cationic-motif-modified exosomes for mRNA delivery to retinal photoreceptors.
Exosome-shuttled miR-150-5p from LPS-preconditioned mesenchymal stem cells down-regulate PI3K/Akt/mTOR pathway via Irs1 to enhance M2 macrophage polarization and confer protection against sepsis.
Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.
Knockdown of NUF2-derived exosomes can inhibit the migration and autophagy of BC cells and improve resistance to doxorubicin.
Enhancing extracellular vesicle cargo loading and functional delivery by engineering protein-lipid interactions.
Advances in preparation and engineering of plant-derived extracellular vesicles for nutrition intervention.
Engineering Versatile Bacteria-Derived Outer Membrane Vesicles: An Adaptable Platform for Advancing Cancer Immunotherapy.
An injectable exosome-loaded hyaluronic acid-polylysine hydrogel for cardiac repair via modulating oxidative stress and the inflammatory microenvironment.
A novel costimulatory molecule gene-modified leukemia cell-derived exosome enhances the anti-leukemia efficacy of DC vaccine in mouse models.

J Nanobiotechnology. 2024 Jul 04. 22(1): 395

Exosome for mRNA delivery: strategies and therapeutic applications.

Zoya Iqbal, Khurrum Rehman, Ayesha Mahmood, Maryam Shabbir, Yujie Liang, Li Duan, Hui Zeng.

  Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.

Keywords:  Exosomes; Targeted delivery; mRNA

DOI:  https://doi.org/10.1186/s12951-024-02634-x
Small Methods. 2024 Jul 05. e2400551

Empowering Exosomes with Aptamers for Precision Theranostics.

Liyan Zheng, Jin Li, Yingying Li, Weidi Sun, LeLe Ma, Fengli Qu, Weihong Tan.

  As information messengers for cell-to-cell communication, exosomes, typically small membrane vesicles (30-150 nm), play an imperative role in the physiological and pathological processes of living systems. Accumulating studies have demonstrated that exosomes are potential biological candidates for theranostics, including liquid biopsy-based diagnosis and drug delivery. However, their clinical applications are hindered by several issues, especially their unspecific detection and insufficient targeting ability. How to upgrade the accuracy of exosome-based theranostics is being widely explored. Aptamers, benefitting from their admirable characteristics, are used as excellent molecular recognition elements to empower exosomes for precision theranostics. With high affinity against targets and easy site-specific modification, aptamers can be incorporated with platforms for the specific detection of exosomes, thus providing opportunities for advancing disease diagnostics. Furthermore, aptamers can be tailored and functionalized on exosomes to enable targeted therapeutics. Herein, this review emphasizes the empowering of exosomes by aptamers for precision theranostics. A brief introduction of exosomes and aptamers is provided, followed by a discussion of recent progress in aptamer-based exosome detection for disease diagnosis, and the emerging applications of aptamer-functionalized exosomes for targeted therapeutics. Finally, current challenges and opportunities in this research field are presented.

Keywords:  aptamers; exosomes; theranostics

DOI:  https://doi.org/10.1002/smtd.202400551
Heliyon. 2024 Jun 15. 10(11): e32376

From bench to bedside: The promising value of exosomes in precision medicine for CNS tumors.

Mengjie Wang, Feng Jin, Xiaoguang Tong.

  Exosomes are naturally present extracellular vesicles (EVs) released into the surrounding body fluids upon the fusion of polycystic and plasma membranes. They facilitate intercellular communication by transporting DNA, mRNA, microRNA, long non-coding RNA, circular RNA, proteins, lipids, and nucleic acids. They contribute to the onset and progression of Central Nervous System (CNS) tumors. In addition, they can be used as biomarkers of tumor proliferation, migration, and blood vessel formation, thereby affecting the Tumor Microenvironment (TME). This paper reviews the recent advancements in the diagnosis and treatment of exosomes in various CNS tumors, the promise and challenges of exosomes as natural carriers of CNS tumors, and the therapeutic prospects of exosomes in CNS tumors. Furthermore, we hope this research can contribute to the development of more targeted and effective treatments for central nervous system tumors.

Keywords:  Biotechnology; CNS tumors; Exosome; Precision treatment; Transit platforms

DOI:  https://doi.org/10.1016/j.heliyon.2024.e32376
Apoptosis. 2024 Jul 03.

Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.

Yiting Geng, Wei Xia, Xiao Zheng, Lujun Chen, You Zhou, Jun Feng, Ye Yuan, Mingyue Zhang, Jianwen Lu, Shanshan Wei, Wenwei Hu.

  BACKGROUND: Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties.RESULTS: By comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level.
CONCLUSION: This study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.

Keywords:  Cetuximab resistance; Colorectal cancer; Engineered exosome; FAK; Paraptosis

DOI:  https://doi.org/10.1007/s10495-024-01986-x
J Mater Chem B. 2024 Jul 01.

Cationic-motif-modified exosomes for mRNA delivery to retinal photoreceptors.

Héctor A Millán Cotto, Tanvi Vinod Pathrikar, Bill Hakim, Helna M Baby, Hengli Zhang, Peng Zhao, Ronak Ansaripour, Rouzbeh Amini, Rebecca L Carrier, Ambika G Bajpayee.

Topical treatment of vitreoretinal diseases remains a challenge due to slow corneal uptake and systemic clearance. Exosomes are emerging nanocarriers for drug delivery due to biocompatibility and cellular targeting properties. To apply them for retinal targeting via the topical route, exosomes must traverse various ocular barriers including the cornea, lens, vitreous humor (VH), and the retina itself. Here we engineered high-purity milk-derived exosomes by anchoring arginine-rich cationic motifs via PEG2000 lipid insertion on their surface. Modification enabled exosomes to use weak-reversible electrostatic interactions with anionic glycosaminoglycan (GAG) and water content of the tissue to enhance their transport rate and retention. Addition of cationic motifs neutralized the anionic surface charge of exosomes (-24 to -2 mV) without impacting size or morphology. Cationic-motif-modified exosomes exhibited two-fold faster steady state diffusivity through bovine corneas compared to unmodified exosomes. Fluorescence recovery after photobleaching confirmed that cationic-motif-modified exosomes can diffuse through VH without steric hindrance. In healthy VH, cationic-motif-modified exosomes demonstrated stronger binding resulting in three-fold lower average diffusivity that enhanced by six-fold in 50% GAG-depleted VH recapitulating advanced liquefaction. Cationic-motif-modified exosomes penetrated through the full-thickness of porcine retinal explants resulting in ten-fold higher uptake in photoreceptors and three-fold greater transfection with encapsulated eGFP mRNA compared to unmodified exosomes. Cationic-motif-modified exosomes are safe to use as they did not adversely affect the mechanical swelling properties of the cornea or lens nor impact retinal cell viability. Cationic-motif-modified exosomes, therefore, offer themselves as a cell-free nanocarrier platform for gene delivery to retinal photoreceptors potentially via the topical route.

DOI: https://doi.org/10.1039/d4tb00849a
Front Immunol. 2024 ;15 1397722

Exosome-shuttled miR-150-5p from LPS-preconditioned mesenchymal stem cells down-regulate PI3K/Akt/mTOR pathway via Irs1 to enhance M2 macrophage polarization and confer protection against sepsis.

Ting Zheng, Sipeng Li, Teng Zhang, Wei Fu, Shuchang Liu, Yuxin He, Xiao Wang, Tao Ma.

  Rationale: Sepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate inflammation during sepsis, and the preconditioning of MSCs could enhance their paracrine potential. Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms.Methods: Exosomes were isolated and characterized from the supernatants of MSCs. The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model. Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the in vivo studies, and to explain the potential mechanisms.
Results: LPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo. In vitro, LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation. miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150-5p in LPS-Exo compared to that in Exo, and exosomal miR-150-5p was transferred into recipient macrophages and mediated macrophage polarization. Further investigation demonstrated that miR-150-5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway.
Conclusion: The current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150-5p as a novel molecular target for regulating immune hyperactivation during sepsis.

Keywords:   sepsis; Irs1; exosomes; macrophage; miR-150-5p

DOI:  https://doi.org/10.3389/fimmu.2024.1397722
J Nanobiotechnology. 2024 Jul 01. 22(1): 382

Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.

Wan-Ting Meng, Jing Zhu, Ya-Chao Wang, Chang-le Shao, Xiu-Ya Li, Ping-Ping Lu, Meng-Ying Huang, Fang-Fang Mou, Hai-Dong Guo, Guang Ji.

  Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.

Keywords:  Inflammatory factors; Milk exosome; Myocardial ischemia-reperfusion injury; NF-κB signaling pathway; Targeting delivery; microRNA-146a

DOI:  https://doi.org/10.1186/s12951-024-02631-0
Tissue Cell. 2024 Jun 21. pii: S0040-8166(24)00156-3. [Epub ahead of print]89 102455

Knockdown of NUF2-derived exosomes can inhibit the migration and autophagy of BC cells and improve resistance to doxorubicin.

Lin Luo, Tong Sha, Hongtao Li.

  Breast cancer (BC) is the most common type of fatal cancer in women. New therapeutic strategies need to be explored to enhance the efficacy of doxorubicin by overcoming the resistance of BC cells. NUF2 is a component of the Ndc80 centromere complex and is a key substance in mediating mitosis and affects the progression of multiple tumors. However, the role as well as mechanisms of NUF2 resistance in BC remain unclear. This study aims to reveal the role of NUF2 in drug resistance in BC. We here revealed that NUF2 was highly expressed in human BC. NUF2 depletion-derived exosomes blocked the growth of BC cells. Further, NUF2 ablation-derived exosomes inhibited autophagy in BC cells. Also, NUF2 ablation-derived exosomes improved doxorubicin resistance in BC cells. Mechanically, NUF2 ablation-derived exosomes blocked PI3K/AKT/mTOR axis in BC cells. In summary, NUF2 ablation-derived exosomes blocked the autophagy of BC cells and improved doxorubicin resistance via mediating PI3K/AKT/mTOR axis.

Keywords:  Autophagy; Breast cancer (BC); Doxorubicin; NUF2; PI3K/AKT/mTOR

DOI:  https://doi.org/10.1016/j.tice.2024.102455
Nat Commun. 2024 Jul 04. 15(1): 5618

Enhancing extracellular vesicle cargo loading and functional delivery by engineering protein-lipid interactions.

Justin A Peruzzi, Taylor F Gunnels, Hailey I Edelstein, Peilong Lu, David Baker, Joshua N Leonard, Neha P Kamat.

Naturally generated lipid nanoparticles termed extracellular vesicles (EVs) hold significant promise as engineerable therapeutic delivery vehicles. However, active loading of protein cargo into EVs in a manner that is useful for delivery remains a challenge. Here, we demonstrate that by rationally designing proteins to traffic to the plasma membrane and associate with lipid rafts, we can enhance loading of protein cargo into EVs for a set of structurally diverse transmembrane and peripheral membrane proteins. We then demonstrate the capacity of select lipid tags to mediate increased EV loading and functional delivery of an engineered transcription factor to modulate gene expression in target cells. We envision that this technology could be leveraged to develop new EV-based therapeutics that deliver a wide array of macromolecular cargo.

DOI: https://doi.org/10.1038/s41467-024-49678-z
Food Chem. 2024 Jun 23. pii: S0308-8146(24)01849-1. [Epub ahead of print]457 140199

Advances in preparation and engineering of plant-derived extracellular vesicles for nutrition intervention.

Caiyun Wu, Jiaxuan Li, Kexin Huang, Xueying Tian, Yaqiong Guo, Andre G Skirtach, Mingliang You, Mingqian Tan, Wentao Su.

  Plant-derived extracellular vesicles (PLEVs), as a type of naturally occurring lipid bilayer membrane structure, represent an emerging delivery vehicle with immense potential due to their ability to encapsulate hydrophobic and hydrophilic compounds, shield them from external environmental stresses, control release, exhibit biocompatibility, and demonstrate biodegradability. This comprehensive review analyzes engineering preparation strategies for natural vesicles, focusing on PLEVs and their purification and surface engineering. Furthermore, it encompasses the latest advancements in utilizing PLEVs to transport active components, serving as a nanotherapeutic system. The prospects and potential development of PLEVs are also discussed. It is anticipated that this work will not only address existing knowledge gaps concerning PLEVs but also provide valuable guidance for researchers in the fields of food science and biomedical studies, stimulating novel breakthroughs in plant-based therapeutic options.

Keywords:  Functional food components; Nano-delivery; Plant-derived extracellular vesicles; Separation; Surface engineering

DOI:  https://doi.org/10.1016/j.foodchem.2024.140199
Adv Sci (Weinh). 2024 Jul 01. e2400049

Engineering Versatile Bacteria-Derived Outer Membrane Vesicles: An Adaptable Platform for Advancing Cancer Immunotherapy.

Ziheng Luo, Xiang Cheng, Bin Feng, Duoyang Fan, Xiaohui Liu, Ruyan Xie, Ting Luo, Seraphine V Wegner, Dayou Ma, Fei Chen, Wenbin Zeng.

  In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

Keywords:  bacterial engineering; cancer immunotherapy; hybrid membrane vesicles; outer membrane vesicles; surface modification

DOI:  https://doi.org/10.1002/advs.202400049
Int J Biol Macromol. 2024 Jul 03. pii: S0141-8130(24)04427-1. [Epub ahead of print] 133622

An injectable exosome-loaded hyaluronic acid-polylysine hydrogel for cardiac repair via modulating oxidative stress and the inflammatory microenvironment.

Yuchen Ren, Weitong Wang, Chaojie Yu, Yue Wang, Yuwei Qiu, Zhiwei Yue, Qingyu Yu, Jiajun Lu, Pengcheng Che, Junjie Li, Hong Sun.

  Myocardial infarction (MI) is a serious cardiovascular disease with complex complications and high lethality. Currently, exosome (Exo) therapy has emerged as a promising treatment of ischemic MI due to its antioxidant, anti-inflammatory, and vascular abilities. However, traditional Exo delivery lacks spatiotemporal precision and targeting of microenvironment modulation, making it difficult to localize the lesion site for sustained effects. In this study, an injectable oxidized hyaluronic acid-polylysine (OHA-PL) hydrogel was developed to conveniently load adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) and improve their retention under physiological conditions. The OHA-PL@Exo hydrogel with high spatiotemporal precision is transplanted minimally invasively into the ischemic myocardium to scavenge intracellular and extracellular reactive oxygen species, regulate macrophage polarization, and attenuate inflammation in the early phase of MI. In addition, this synergistic microenvironment modulation can effectively reduce myocardial fibrosis and ventricular remodeling, promote angiogenesis, and restore electrophysiological function in the late stage of MI. Therefore, this hyaluronic acid-polylysine to deliver exosomes has become a promising therapeutic strategy for myocardial repair.

Keywords:  Antioxidant hydrogels; Exosomes; Macrophage polarization; Myocardial repair

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.133622
Vaccine. 2024 Jul 02. pii: S0264-410X(24)00738-2. [Epub ahead of print]

A novel costimulatory molecule gene-modified leukemia cell-derived exosome enhances the anti-leukemia efficacy of DC vaccine in mouse models.

Difan Zhang, Yan Jiang, Minghui Wang, Jie Zhao, Jiangbo Wan, Zhichao Li, Dan Huang, Jing Yu, Jiaqi Li, Jiayu Liu, Fang Huang, Siguo Hao.

  OBJECTIVES: Leukemia cell-derived exosomes (LEXs), carrying leukemia cell-specific antigens, can serve as a source of antigen for dendritic cell (DC) vaccine loading. However, LEX-targeted DC-based vaccines have demonstrated limited antitumor immune effects in clinical trials, attributed to the low immunogenicity of LEXs and the scant levels of costimulatory molecules on DCs. The costimulatory molecules CD80 and CD86, which are crucial to DC function, play a significant role in enhancing immune efficacy. In this study, we explored the anti-leukemia immune response of costimulatory molecule gene-modified LEX-targeted DCs (LEX-8086) in vitro and in animal models.METHODS: DCs were incubated with LEX-8086 to produce LEX-8086-targeted DCs (DCsLEX-8086). ELISA, cytotoxicity assays and flow cytometry utilized to assess the antitumor efficacy of DCsLEX8086 in vitro. Flow cytometry was used to evaluate the immunomodulatory function of DCsLEX8086 in animal models.
RESULTS: Our findings indicated that LEX-8086 enhanced the maturation and antigen-presenting ability of DCs. Immunization with DCsLEX8086 significantly activated CD8+ T cells and boosted the CTL response in vitro. More importantly, DCsLEX-8086 effectively suppressed tumor growth and exerted anti-leukemia effects in both prophylactic and therapeutic animal models. Furthermore, DCsLEX-8086 promoted the proportion of CD4+ T cells, CD8+ T cells and M1 macrophages in the tumor environments both prophylactically and therapeutically. Treatment with DCsLEX-8086 showed no significant difference in the levels of M2 macrophages but decreased the proportion of Tregs within the tumor bed during therapeutic experiments.
CONCLUSION: The results suggested that DCsLEX-8086 induces a more effective anti-leukemia immunity compared to DCsLEX-null in vivo and in vitro. DCsLEX-8086 might achieve antitumor effects by elevating the numbers of CD4+ T cells, CD8+ T cells, and M1 macrophages in tumors. Our findings indicate that DCsLEX-8086 could be leveraged to develop a new, highly effective vaccine for anti-leukemia immunity.

Keywords:  Antileukemia effects; B7 costimulatory molecules; Gene-modified leukemia-derived exosomes; LEX-targeted dendritic cell vaccines

DOI:  https://doi.org/10.1016/j.vaccine.2024.06.064