Antitumor Vaccines Research Articles

Melanoma-specific antigen-associated antitumor antibody reactivity as an immune-related biomarker for targeted immunotherapies

Background:Immunotherapies, including cancer vaccines and immune checkpoint inhibitors have transformed the management of many cancers. However, a large number of patients show resistance to these immunotherapies and current research has provided limited findings for predicting response to precision immunotherapy treatments.Methods:Here, we applied the next generation phage display mimotope variation analysis (MVA) to profile antibody response and dissect the role of humoral immunity in targeted cancer therapies, namely anti-tumor dendritic cell vaccine (MelCancerVac®) and immunotherapy with anti-PD-1 monoclonal antibodies (pembrolizumab).Results:Analysis of the antibody immune response led to the characterization of epitopes that were linked to melanoma-associated and cancer-testis antigens (CTA) whose antibody response was induced upon MelCancerVac® treatments of lung cancer. Several of these epitopes aligned to antigens with strong immune response in patients with unresectable metastatic melanoma receiving anti-PD-1 therapy.Conclusions:This study provides insights into the differences and similarities in tumor-specific immunogenicity related to targeted immune treatments. The antibody epitopes as biomarkers reflect melanoma-associated features of immune response, and also provide insights into the molecular pathways contributing to the pathogenesis of cancer. Concluding, antibody epitope response can be useful in predicting anti-cancer immunity elicited by immunotherapy.

Dendritic cells metabolism: a strategic path to improve antitumoral DC vaccination.

The critical role developed by dendritic cell (DC) in the orchestration of immune response explains its exploitation in different therapeutic approaches as potential vaccine tools. Various clinical trials dissect its role in different types of solid cancers. However, there is a lack of comprehension regarding the potential impact of DC metabolic pathways on the effectiveness of DC vaccine. In this review, we intend to dissect how metabolism could be a critical component of DC vaccine formulation, exploring opportunities to improve: (i) processing and cross-presentation of tumour antigens; (ii) DC migration, and (iii) DC immunogenic profile. Overall, we aim to open the discussion to explore new avenues/paths where DC metabolism might be considered a core component of antitumour DC vaccine with this review.

Immunotherapy in the complex treatment of tumor diseases

The purpose of the study was to identify and analyze the potential of immunotherapy aimed at enhancing the immune system’s ability to resist tumor development and (or) weakening the ability of the tumor to maintain its growth.Material and methods. A search for available literature sources published in Medline, Pubmed, etc. Databases was made. We found 215 publications regarding the study of the formation of antitumor mechanisms, of which 57 were included in this review.Results. The review was devoted to the analysis of the literature on tumor growth suppression by modulating inflammation, correcting the concentration of factors and enzymes, inhibiting the formation of immunosuppressive cells, enhancing antibody cytotoxicity, and stimulating cellular cytotoxicity. The feasibilities of antitumor vaccination were evaluated.Conclusion. Different immunotherapeutic effects were found can enhance the antitumor effect of each other. In the early stages of the disease, immunotherapy can eliminate tumor cells remaining in the body after surgical removal of the primary tumor. In the advanced stages of the disease, combined treatment, including traditional cytoreductive and immunotherapeutic treatment, should be aimed at inhibiting the development of the disease. The prognosis of the disease can be assessed on an inflammatory scale based on the determination of 3 blood parameters: the content of c-reactive protein, the level of lactate dehydrogenase, and the determination of the neutrophil-lymphocyte ratio.

Efficacy of instillation of MB49 cells and thermoreversible polymeric gel in urothelial bladder carcinoma immunization.

BackgroundActivating the immune system for therapeutic benefit has long been a goal in immunology, especially in cancer treatment, but the low immunogenicity of antitumor vaccines remains a limiting factor in the fight against malignant neoplasms. The increase in the immunogenicity of weak antigens using biodegradable polymers, such as chitosan, has been observed in the field of cancer immunotherapy. However, the effects of the vaccine using a combination of tumor cells and a thermoreversible delivery system based on chitosan in bladder cancer models, mainly using the intravesical route to stimulate the antitumor immune response, are unknown. We propose to evaluate the efficacy of a polymeric gel matrix (TPG) formed by poloxamer 407 and chitosan, associated with MB49 cells, as an intravesical antitumor vaccine using a C57BL/6 murine model of bladder urothelial carcinoma. The effectiveness of immunization was analyzed with the formation of three experimental groups: Control, TPG and TPG + MB49. In the vaccination phase, the TPG + MB49 group underwent a traumatic injury to the bladder wall with immediate intravesical instillation of the vaccine compound containing MB49 cells embedded in TPG. The TPG group was subjected to the same procedures using the compound containing the gel diluted in medium, and the control group using only the medium. After 21 days, the animals were challenged with tumor induction. ResultsIn vitro tests showed loss of viability and inability to proliferate after exposure to TPG. In vivo tests showed that animals previously immunized with TPG + MB49 had higher cumulative survival, as well as significantly lower bladder weight and size in contrast to the other two groups that did not show a statistically different tumor evolution. In addition, the splenocytes of these animals also showed a higher rate of antitumor cytotoxicity in relation to the TPG and control groups. ConclusionsWe can conclude that MB49 cells embedded in a polymeric thermoreversible gel matrix with chitosan used in the form of an intravesical vaccine are able to stimulate the immune response and affect the development of the bladder tumor in an orthotopic and syngeneic C57BL/6 murine model.

RNA origami as a vaccine assembly platform to promote CD8 T Cell mediated anti-tumor immunity

Abstract CD8 T cell mediated immunity is critical for controlling tumor growth. However, constructing synthetic vaccines that can effectively induce this arm of the immunity has been challenging. With the advancement of nanotechnologies, various nanostructures have been explored to link antigens and adjuvants together for increased stability, lymph node delivery, cellular uptake, and activation of innate immunity, all of which may help elicit potent T cell responses against tumors. Here, we explored a self-assembling RNA origami (RNA-OG) nanostructure as a vaccine platform to assemble tumor antigens. In addition to acting as an antigen carrier, RNA-OG is an intrinsic TLR3 agonist and therefore functions as a potent adjuvant. Thus, these RNA-OG-antigen vaccines offer simultaneous delivery of antigens and adjuvants for better initiation of T-cell mediated immunity. We demonstrated enhanced antigen cross-presentation of RNA-OG-linked antigens by dendritic cells and subsequent induction of antigen-specific CD8-T cell responses. Using B16-OVA (ovalalbumin) murine melanoma tumor model, RNA-OG-OVA vaccines induced an anti-tumor immune response that contributed to long-term tumor immunity and increased survival of the animals. Overall, our data demonstrates that RNA-OG can function as a potent anti-tumor vaccine platform.

Anti-tumor immunity by transcriptional synergy between TLR9 and STING activation.

Agonists for TLR9 and stimulator of IFN genes (STING) offer therapeutic applications as both anti-tumor agents and vaccine adjuvants, though their clinical applications are limited; the clinically available TLR9 agonist is a weak IFN inducer and STING agonists induce undesired type 2 immunity. Yet, combining TLR9 and STING agonists overcame these limitations by synergistically inducing innate and adaptive IFNγ to become an advantageous type 1 adjuvant, suppressing type 2 immunity, in addition to exerting robust anti-tumor activities when used as a monotherapeutic agent for cancer immunotherapy. Here, we sought to decipher the immunological mechanisms behind the synergism mediated by TLR9 and STING agonists and found that their potent anti-tumor immunity in a Pan02 peritoneal dissemination model of pancreatic cancer was achieved only when agonists for TLR9 and STING were administered locally, and was via mechanisms involving CD4 and CD8 T cells as well as the co-operative action of IL-12 and type I IFNs. Rechallenge studies of long-term cancer survivors suggested that the elicitation of Pan02-specific memory responses provides protection against the secondary tumor challenge. Mechanistically, we found that TLR9 and STING agonists synergistically induce IL-12 and type I IFN production in murine APCs. The synergistic effect of the TLR9 and STING agonists on IL-12p40 was at protein, mRNA and promoter activation levels, and transcriptional regulation was mediated by a 200 bp region situated 983 bp upstream of the IL-12p40 transcription initiation site. Such intracellular transcriptional synergy may hold a key in successful cancer immunotherapy and provide further insights into dual agonism of innate immune sensors during host homeostasis and diseases.

In Situ Tumor Vaccination with Calcium-Linked Degradable Coacervate Nanocomplex Co-Delivering Photosensitizer and TLR7/8 Agonist to Trigger Effective Anti-Tumor Immune Responses.

In situ anti-tumor vaccination is an attractive type of cancer immunotherapy which relies on the effectiveness of dendritic cells (DCs) to engulf tumor antigens, become activated, and present antigens to T cells in lymphoid tissue. Here, a multifunctional nanocomplex based on calcium crosslinked polyaspartic acid conjugated to either a toll-like receptor (TLR)7/8 agonist or a photosensitizer is reported. Intratumoral administration of the nanocomplex followed by laser irradiation induces cell killing and hence generation of a pool of tumor-associated antigens, with concomitant promotion of DCs maturation and expansion of T cells in tumor-draining lymph nodes. Suppression of tumor growth is observed both at the primary site and at the distal site, thereby hinting at successful induction of an adaptive anti-tumor response. This strategy holds promise for therapeutic application in a pre-operative and post-operative setting to leverage to mutanome of the patient's own tumor to mount immunological memory to clear residual tumor cells and metastasis.

Toll-like receptor agonist combinations augment mouse T-cell anti-tumor immunity via IL-12- and interferon ß-mediated suppression of immune checkpoint receptor expression

ABSTRACT We previously found that activated CD8+ T-cells increase expression of PD-1, which can be attenuated in the presence of specific Toll-like receptor (TLR) agonists, mediated by IL-12 secreted by professional antigen-presenting cells. While these CD8+ T-cells had greater anti-tumor activity, T-cells stimulated by different TLR had different gene expression profiles. Consequently, we sought to determine whether combinations of TLR agonists might further affect the expression of T-cell checkpoint receptors and improve T-cell anti-tumor immunity. Activation of CD8+ T-cells in the presence of specific TLR ligands resulted in decreased expression of PD-1, LAG-3, and CD160, notably with combinations of TLR1/2, TLR3, and TLR9 agonists. Immunization of E.G7-OVA or TRAMP-C1 tumor-bearing mice with peptide or DNA vaccines, co-administered with combination of TLR3 and TLR9 agonists, showed greater suppression of tumor growth. The anti-tumor effect of TLR1/2 and/or TLR9, but not TLR3, was abrogated in IL-12KO mice. RNA sequencing of TLR-conditioned CD8+ T-cells revealed IL-12 pathway activation, and type 1 IFN pathway activation following TLR3 stimulation. Our results provide a mechanistic rationale for the choice of optimal combinations of TLR ligands to use as adjuvants to improve the efficacy of anti-tumor vaccines.

Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine.

The tumor-associated antigen mucin 1 (MUC1) is an attractive target of antitumor vaccine, but its weak immunogenicity is a big challenge for the development of vaccine. In order to enhance immune responses against MUC1, herein, we conjugated small molecular toll-like receptor 7 agonist (TLR7a) to carrier protein BSA via MUC1 glycopeptide to form a three-component conjugate (BSA-MUC1-TLR7a). Furthermore, we combined the three-component conjugate with Alum adjuvant to explore their synergistic effects. The immunological studies indicated that Alum adjuvant and built-in TLR7a synergistically enhanced anti-MUC1 antibody responses and showed Th1-biased immune responses. Meanwhile, antibodies elicited by the vaccine candidate effectively recognized tumor cells and induced complement-dependent cytotoxicity. In addition, Alum adjuvant and built-in TLR7a synergistically enhanced MUC1 glycopeptide-specific memory CD8+ T-cell immune responses. More importantly, the vaccine with the binary adjuvant can significantly inhibit tumor growth and prolong the survival time of mice in the tumor challenge experiment. This novel vaccine construct provides an effective strategy to develop antitumor vaccines.

MUC1 Specific Immune Responses Enhanced by Coadministration of Liposomal DDA/MPLA and Lipoglycopeptide.

Mucin 1 (MUC1), a well-known tumor-associated antigen and attractive target for tumor immunotherapy, is overexpressed in most human epithelial adenomas with aberrant glycosylation. However, its low immunogenicity impedes the development of MUC1-targeted antitumor vaccines. In this study, we investigated three liposomal adjuvant systems containing toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and auxiliary lipids of different charges: cationic lipid dimethyldioctadecylammonium (DDA), neutral lipid distearoylglycerophosphocholine (DSPC) or anionic lipid dioleoylphosphatidylglycerol (DOPG), respectively. ELISA assay evidenced that the positively charged DDA/MPLA liposomes are potent immune activators, which induced remarkable levels of anti-MUC1 antibodies and exhibited robust Th1-biased immune responses. Importantly, the antibodies induced by DDA/MPLA liposomes efficiently recognized and killed MUC1-positive tumor cells through complement-mediated cytotoxicity. In addition, antibody titers in mice immunized with P2-MUC1 vaccine were significantly higher than those from mice immunized with P1-MUC1 or MUC1 vaccine, which indicated that the lipid conjugated on MUC1 antigen also played important role for immunomodulation. This study suggested that the liposomal DDA/MPLA with lipid-MUC1 is a promising antitumor vaccine, which can be used for the immunotherapy of various epithelial carcinomas represented by breast cancer.

Systemically Administered TLR7/8 Agonist and Antigen-Conjugated Nanogels Govern Immune Responses against Tumors.

The generation of specific humoral and cellular immune responses plays a pivotal role in the development of effective vaccines against tumors. Especially the presence of antigen-specific, cytotoxic T cells influences the outcome of therapeutic cancer vaccinations. Different strategies, ranging from delivering antigen-encoding mRNAs to peptides or full antigens, are accessible but often suffer from insufficient immunogenicity and require immune-boosting adjuvants as well as carrier platforms to ensure stability and adequate retention. Here, we introduce a pH-responsive nanogel platform as a two-component antitumor vaccine that is safe for intravenous application and elicits robust immune responses in vitro and in vivo. The underlying chemical design allows for straightforward covalent attachment of a model antigen (ovalbumin) and an immune adjuvant (imidazoquinoline-type TLR7/8 agonist) onto the same nanocarrier system. In addition to eliciting antigen-specific T and B cell responses that outperform mixtures of individual components, our two-component nanovaccine leads in prophylactic and therapeutic studies to an antigen-specific growth reduction of different tumors expressing ovalbumin intracellularly or on their surface. Regarding the versatile opportunities for functionalization, our nanogels are promising for the development of highly customized and potent nanovaccines.

Enhancing the anti-leukemia immunity of acute lymphocytic leukemia-derived exosome-based vaccine by downregulation of PD-L1 expression.

Cell-released nanovesicles can induce anti-leukemia immunity. Leukemia cell-derived exosomes (LEXs) are promising anti-tumor vaccine components for cancer immunotherapy. Nonetheless, LEX-based vaccines show modest potency in vivo, likely due to the presence of immunosuppressive PD-L1 proteins in the exosomes. We hypothesized that targeting exosomal PD-L1 could optimize LEX-based vaccines. To test this hypothesis, we compared the capacity of exosomes derived from PD-L1-silenced acute lymphocytic leukemia-derived leukemia cells (LEXPD-L1si) and non-modified exosomes to induce anti-leukemia immunity. Lentivirus-mediated PD-L1 shRNA was used to downregulate PD-L1 expression in parental leukemia cells and LEXs. LEXPD-L1si were characterized by electron microscopy, Western blotting, nanoparticle tracking analysis and flow cytometry, and their anti-leukemia immune effects were tested on immune cells and in animal models. In the present study, lentivirus-mediated PD-L1 shRNA successfully downregulated PD-L1 expression in parental leukemia cells and in LEXs. LEXPD-L1si induced better DC maturation and subsequently enhanced T cell activation, as compared with non-modified LEXs. Consistently, immunization with LEXPD-L1si induced greater T cell proliferation and Th1 cytokine release. LEXPD-L1si was a more potent inducer of antigen-specific cytotoxic lymphocyte (CTL) response. Finally, we vaccinated DBA/2 mice with exosome formulations to test their ability to induce both protective and therapeutic anti-tumor CTL responses in vivo. Vaccination with LEXPD-L1si strongly inhibited tumor growth and prolonged survival of immunized mice. Downregulation of exosomal PD-L1 expression in LEXs effectively induces more potent anti-leukemia immunity. Therefore, our strategy for optimizing LEX-based vaccine has a potential application in leukemia immunotherapy.

Tumor-associated Exosomes Are Involved in Hepatocellular Carcinoma Tumorigenesis, Diagnosis, and Treatment.

Hepatocellular carcinoma (HCC) has become a challenging disease worldwide. There are still limitations in the diagnosis and treatment of HCC, and its high metastatic capacity and high recurrence rate are the main reasons for its poor prognosis. The ability of extracellular vesicles (EVs) to transfer functionally-active substances and their widespread presence in almost all body fluids suggest their unprecedented potential in the study of various cancers. The unique physicochemical properties of EVs determine their potential as antitumor vaccines and drug carriers. In the last decade, the study of EVs in HCC has evolved from a single hot topic to a system with considerable scale. This paper summarizes the role of EVs, especially exosomes, in the occurrence, metastasis and tumor immunity of HCC, reviews their applications in tumor diagnosis, prognosis and treatment, describes the pros and cons of these studies, and looks forward towards the future research directions of EVs in HCC.

Antitumor Peptide-Based Vaccine in the Limelight.

The success of the immune checkpoint blockade has provided a proof of concept that immune cells are capable of attacking tumors in the clinic. However, clinical benefit is only observed in less than 20% of the patients due to the non-specific activation of immune cells by the immune checkpoint blockade. Developing tumor-specific immune responses is a challenging task that can be achieved by targeting tumor antigens to generate tumor-specific T-cell responses. The recent advancements in peptide-based immunotherapy have encouraged clinicians and patients who are struggling with cancer that is otherwise non-treatable with current therapeutics. By selecting appropriate epitopes from tumor antigens with suitable adjuvants, peptides can elicit robust antitumor responses in both mice and humans. Although recent experimental data and clinical trials suggest the potency of tumor reduction by peptide-based vaccines, earlier clinical trials based on the inadequate hypothesis have misled that peptide vaccines are not efficient in eliminating tumor cells. In this review, we highlighted the recent evidence that supports the rationale of peptide-based antitumor vaccines. We also discussed the strategies to select the optimal epitope for vaccines and the mechanism of how adjuvants increase the efficacy of this promising approach to treat cancer.

A self-adjuvanting anti-tumor nanoliposomal vaccine based on fluorine-substituted MUC1 glycopeptide.

Herein, a self-adjuvanting fluorinated MUC1-based nanoliposomal antitumor vaccine was constructed for the first time. Both the tumor-associated antigen and the mode of its presentation affect the immune response for antitumor vaccines.

Selection of the most immunogenic antigen for DNA vaccination against neuroblastoma

Evaluation of the antigen immunogenicity is one of the initial steps in selecting an effective target for antitumor vaccination. This is most relevant for tumors that have no specific markers or have a weak mutational status like neuroblastoma. The purpose of this study is to select the most immunogenic antigen for DNA vaccination against neuroblastoma and to conduct a comparative analysis of predictive programs and a mouse model. To assess the immunogenicity C57Bl/6 female mice 8-10 weeks of age (n=25) were used. The mice received two vaccinations with a DNA construct based on tyrosine hydroxylase, Birc5, and Phox2b antigens. On the 28th day, the spleens were removed and the cytotoxic activity of splenocytes and the level of production ofIFNγ were assessed. The highest levels of cytotoxic activity (18.4%) and IFNγ (60% of those responding to stimulation) were observed after vaccination with Phox2b. Thus, the most immunogenic antigen according to IEDB showed the best results in the mouse model and can be further used for DNA vaccination in neuroblastoma.

Immunomodulatory Effects of Extract of Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Basidiocarps Cultivated on Alternative Substrate.

Ganoderma lucidum is a medicinal mushroom exhibiting numerous health benefits primarily based on strong immunostimulatory effects. The study aimed to investigate if there were differences in effects of extracts of commercially (GC) and alternatively (wheat straw) (GA) cultivated G. lucidum basidiocarps on properties of peritoneal macrophages (PM) and monocyte-derived dendritic cells (MoDCs). Differences in immunomodulatory effects of GC/GA extracts were studied. The viability of treated PMs, their adhesive and phagocytic capability, and their capacity to produce reactive oxygen species (ROS) and NO were tested. Immature MoDCs generated from human monocytes were treated with poly I:C (10.0 μg/ml) and loxoribine (34.0 μg/ml), a selective TLR3 and TLR7 agonists, respectively, and with/without GC/GA extract (100.0 μg/ml). The effect of each combination on phenotypic properties, cytokines production by MoDCs, and their proliferation and Th polarizing capacity was studied. GA extract stimulated the metabolic and phagocytic activity of PMs, their adhesion capability, and ability to produce ROS and NO more strongly compared to GC. Both tested extracts significantly increased allostimulatory and Th1 polarization capacity of simultaneous TLR3 and TLR7-activated MoDCs, but GA extract was more effective. The extract of alternatively cultivated G. lucidum basidiocarps increased production of ROS and NO by TLR4 stimulated PMs and upregulated production of certain cytokines as well as allostimulatory and Th1 polarization capacity of MoDCs. GA extract could be a potent immunostimulatory agent for activation of MoDCs with the simultaneous engagement of TLRs, which seems to be a promising strategy for the preparation of DC-based anti-tumor vaccines.

Active immunization combined with cisplatin confers enhanced therapeutic protection and prevents relapses of HPV-induced tumors at different anatomical sites.

The active immunotherapy concept relies on the use of vaccines that are capable of inducing antitumor immunity, reversion of the suppressive immunological environment, and long-term memory responses. Previously, antitumor vaccines based on a recombinant plasmid (pgDE7h) or a purified protein (gDE7) led to regression of early-established human papillomavirus (HPV)-associated tumors in a preclinical model. In this work, the anticancer vaccines were combined with cisplatin to treat HPV-induced tumors at advanced growth stages. The antitumor effects were evaluated in terms of tumor regression, induction of specific CD8+ T cells, and immune modulation of the tumor microenvironment. Acute toxicity induced by the treatment was measured by weight loss and histological alterations in the liver and kidneys. Our results revealed that the combination of cisplatin with either one of the tested immunotherapies (pgDE7h or gDE7) led to complete tumor regression in mice. Also, the combined treatment resulted in synergistic effects, particularly among mice immunized with gDE7, including activation of systemic and tumor-infiltrating E7-specific CD8+ T cells, tumor infiltration of macrophages and dendritic cells, and prevention of tumor relapses at different anatomical sites. Furthermore, the protocol allowed the reduction of cisplatin dosage and its intrinsic toxic effects, without reducing antitumor outcomes. These results expand our knowledge of active immunotherapy protocols and open perspectives for alternative treatments of HPV-associated tumors.

Pseudocowpox virus, a novel vector to enhance the therapeutic efficacy of antitumor vaccination.

ObjectiveAntitumor viral vaccines, and more particularly poxviral vaccines, represent an active field for clinical development and translational research. To improve the efficacy and treatment outcome, new viral vectors are sought, with emphasis on their abilities to stimulate innate immunity, to display tumor antigens and to induce a specific T‐cell response.MethodsWe screened for a new poxviral backbone with improved innate and adaptive immune stimulation using IFN‐α secretion levels in infected PBMC cultures as selection criteria. Assessment of virus effectiveness was made in vitro and in vivo.ResultsThe bovine pseudocowpox virus (PCPV) stood out among several poxviruses for its ability to induce significant secretion of IFN‐α. PCPV produced efficient activation of human monocytes and dendritic cells, degranulation of NK cells and reversed MDSC‐induced T‐cell suppression, without being offensive to activated T cells. A PCPV‐based vaccine, encoding the HPV16 E7 protein (PCPV‐E7), stimulated strong antigen‐specific T‐cell responses in TC1 tumor‐bearing mice. Complete regression of tumors was obtained in a CD8+ T‐cell‐dependent manner after intratumoral injection of PCPV‐E7, followed by intravenous injection of the cancer vaccine MVA‐E7. PCPV also proved active when injected repeatedly intratumorally in MC38 tumor‐bearing mice, generating tumor‐specific T‐cell responses without encoding a specific MC38 antigen. From a translational perspective, we demonstrated that PCPV‐E7 effectively stimulated IFN‐γ production by T cells from tumor‐draining lymph nodes of HPV+‐infected cancer patients.ConclusionWe propose PCPV as a viral vector suitable for vaccination in the field of personalised cancer vaccines, in particular for heterologous prime‐boost regimens.

Immune Cell-Derived Extracellular Vesicles - New Strategies in Cancer Immunotherapy.

Immune cell-derived extracellular vesicles (EVs) have increasingly become the focus of research due to their unique characteristics and bioinspired applications. They are lipid bilayer membrane nanosized vesicles harboring a range of immune cell-derived surface receptors and effector molecules from parental cells. Immune cell-derived EVs are important mediators of intercellular communication that regulate specific mechanisms of adaptive and innate immune responses. However, the mechanisms underlying the antitumor effects of EVs are still being explored. Importantly, immune cell-derived EVs have some unique features, including accessibility, storage, ability to pass through blood-brain and blood-tumor barriers, and loading of various effector molecules. Immune cell-derived EVs have been directly applied or engineered as potent antitumor vaccines or for the diagnosis of clinical diseases. More research applications involving genetic engineering, membrane engineering, and cargo delivery strategies have improved the treatment efficacy of EVs. Immune cell-derived EV-based therapies are expected to become a separate technique or to complement immunotherapy, radiotherapy, chemotherapy and other therapeutic modalities. This review aims to provide a comprehensive overview of the characteristics and functions of immune cell-derived EVs derived from adaptive (CD4+ T, CD8+ T and B cells) and innate immune cells (macrophages, NK cells, DCs, and neutrophils) and discuss emerging therapeutic opportunities and prospects in cancer treatment.