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Biomaterials Nov 2023Cancer vaccine holds vast promise in potentiating tumor immunotherapy. Here, we developed a simple cancer vaccine based on the liquid nitrogen-treated cells (LNT cells)...
Cancer vaccine holds vast promise in potentiating tumor immunotherapy. Here, we developed a simple cancer vaccine based on the liquid nitrogen-treated cells (LNT cells) that engineered by one-shot shocking of the live tumor cells in liquid nitrogen. In this vaccine, the obtained LNT cells served as both tumor antigens and delivery vehicles to load the adjuvant imiquimod (R837). This design could achieve efficient co-uptake of antigen/adjuvant by antigen presenting cells (APCs) and prolong in vivo retention of tumor antigens and adjuvants. This adjuvant-loaded LNT cells augmented in vivo antitumor responses and enhanced survival in melanoma-bearing mouse model compared with conventional whole-cell vaccine of the mixture of tumor lysis and adjuvant.
Topics: Mice; Animals; Cancer Vaccines; Adjuvants, Immunologic; Immunotherapy; Antigens, Neoplasm; Melanoma; Vaccination; Nitrogen; Dendritic Cells
PubMed: 37741150
DOI: 10.1016/j.biomaterials.2023.122319 -
Frontiers in Immunology 2023Allergen-specific immunotherapy (AIT) describes the establishment of peripheral tolerance through repeated allergen exposure, which qualifies as the only curative... (Review)
Review
Allergen-specific immunotherapy (AIT) describes the establishment of peripheral tolerance through repeated allergen exposure, which qualifies as the only curative treatment for allergic diseases. Although conventional subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have been approved to treat respiratory allergies clinically, the progress made is far from satisfactory. Epicutaneous immunotherapy (EPIT) exploits the skin's immune properties to modulate immunological response, which is emerging as a promising alternative and has shown effectiveness in many preclinical and clinical studies for both respiratory and food allergies. It is worth noting that the stratum corneum (SC) barrier impedes the effective delivery of allergens, while disrupting the SC layer excessively often triggers unexpected Th2 immune responses. This work aims to comprehend the immunological mechanisms of EPIT, and summarize the innovative system for sufficient delivery of allergens as well as tolerogenic adjuvants. Finally, the safety, acceptability, and cost-effectiveness of these innovative delivery systems are discussed, which directs the development of future immunotherapies with all desirable characteristics.
Topics: Humans; Hypersensitivity; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Desensitization, Immunologic; Epidermis
PubMed: 37675117
DOI: 10.3389/fimmu.2023.1238022 -
Medicinal Research Reviews Jul 2024Adjuvants are of critical value in vaccine development as they act on enhancing immunogenicity of antigen and inducing long-lasting immunity. However, there are only a... (Review)
Review
Adjuvants are of critical value in vaccine development as they act on enhancing immunogenicity of antigen and inducing long-lasting immunity. However, there are only a few adjuvants that have been approved for clinical use, which highlights the need for exploring and developing new adjuvants to meet the growing demand for vaccination. Recently, emerging evidence demonstrates that the cGAS-STING pathway orchestrates innate and adaptive immunity by generating type I interferon responses. Many cGAS-STING pathway agonists have been developed and tested in preclinical research for the treatment of cancer or infectious diseases with promising results. As adjuvants, cGAS-STING agonists have demonstrated their potential to activate robust defense immunity in various diseases, including COVID-19 infection. This review summarized the current developments in the field of cGAS-STING agonists with a special focus on the latest applications of cGAS-STING agonists as adjuvants in vaccination. Potential challenges were also discussed in the hope of sparking future research interests to further the development of cGAS-STING as vaccine adjuvants.
Topics: Humans; Nucleotidyltransferases; Membrane Proteins; Animals; Adjuvants, Vaccine; Signal Transduction; COVID-19; SARS-CoV-2; Immunity, Innate; Adjuvants, Immunologic; COVID-19 Vaccines
PubMed: 38323921
DOI: 10.1002/med.22016 -
International Immunopharmacology Dec 2023To improve antigen immunogenicity and promote long-lasting immunity, vaccine formulations have been appropriately supplemented with adjuvants. Graphene has been found to... (Review)
Review
To improve antigen immunogenicity and promote long-lasting immunity, vaccine formulations have been appropriately supplemented with adjuvants. Graphene has been found to enhance the presentation of antigens to CD8+ T cells, as well as stimulating innate immune responses and inflammatory factors. Its properties, such as large surface area, water stability, and high aspect ratio, make it a suitable candidate for delivering biological substances. Graphene-based nanomaterials have recently attracted significant attention as a new type of vaccine adjuvants due to their potential role in the activation of immune responses. Due to the limited functionality of some approved human adjuvants for use, the development of new all-purpose adjuvants is urgently required. Research on the immunological and biomedical use of graphene oxide (GO) indicates that these nanocarriers possess excellent physicochemical properties, acceptable biocompatibility, and a high capacity for drug loading. Graphene-based nanocarriers also could improve the function of some immune cells such as dendritic cells and macrophages through specific signaling pathways. However, GO injection can lead to significant oxidative stress and inflammation. Various surface functionalization protocols have been employed to reduce possible adverse effects of GO, such as aggregation of GO in biological liquids and induce cell death. Furthermore, these modifications enhance the properties of functionalized-GO's qualities, making it an excellent carrier and adjuvant. Shedding light on different physicochemical and structural properties of GO and its derivatives has led to their application in various therapeutic and drug delivery fields. In this review, we have endeavored to elaborate on different aspects of GO.
Topics: Humans; Adjuvants, Vaccine; Graphite; Adjuvants, Immunologic; Pharmaceutical Preparations
PubMed: 37866317
DOI: 10.1016/j.intimp.2023.111062 -
Scientific Reports Sep 2023Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although...
Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although non-metastatic EWS is typically responsive to treatment when newly diagnosed, relapsed cases have an unmet need for which no standard treatment approach exists. Recent phase III clinical trials for EWS comparing 7 vs 5 chemotherapy drugs have failed to improve survival. To extend the durability of remission for EWS, we investigated 3 non-chemotherapy adjuvant therapy drug candidates to be combined with chemotherapy. The efficacy of these adjuvant drugs was investigated via anchorage-dependent growth assays, anchorage-independent soft-agar colony formation assays and EWS xenograft mouse models. Enoxacin and entinostat were the most effective adjuvant drug in both long-term in vitro and in vivo adjuvant studies. In the context that enoxacin is an FDA-approved antibiotic, and that entinostat is an investigational agent not yet FDA-approved, we propose enoxacin as an adjuvant drug for further preclinical and clinical investigation in EWS patients.
Topics: Humans; Animals; Mice; Sarcoma, Ewing; Enoxacin; Neuroectodermal Tumors, Primitive, Peripheral; Benzamides; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Disease Models, Animal; Tumor Suppressor Protein p53
PubMed: 37658148
DOI: 10.1038/s41598-023-40751-z -
Annals of Medicine Dec 2023Amyloid light chain (AL) amyloidosis is the most common systemic amyloidosis. The objective of this scoping review was to map the available literature on the diagnosis... (Review)
Review
BACKGROUND
Amyloid light chain (AL) amyloidosis is the most common systemic amyloidosis. The objective of this scoping review was to map the available literature on the diagnosis of AL amyloidosis in China.
MATERIALS AND METHODS
The published academic papers related to the diagnosis of AL amyloidosis were screened from 1 January 2000 to 15 September 2021. Chinese patients who have suspected AL amyloidosis were included. The included studies were categorized into accuracy studies and descriptive studies based on if the studies supplied the diagnostic accuracy data or not. The information on the diagnostic methods reported by included studies was synthesized.
RESULTS
Forty-three articles were included for the final scoping review, with 31 belonging to descriptive studies and 12 having information on diagnostic accuracy. Although cardiac involvement was second top in Chinese patients with AL amyloidosis, a cardiac biopsy was rare. Next, we found light chain classification and monoclonal (M-) protein identification were essential methods for the diagnosis of AL amyloidosis in China. In addition, some combined tests (e.g. immunohistochemistry and serum free light chain, immunohistochemistry and immunofixation electrophoresis, and serum free light chain and immunofixation electrophoresis) can increase the sensitivity of the diagnosis. Finally, several adjuvant methods (e.g. Imaging, N-terminal-pro hormone BNP, and brain natriuretic peptide test) were important for AL amyloidosis diagnosis.
CONCLUSION
This scoping review details the characteristics and results of the recently published studies on diagnosing AL Amyloidosis in China. Biopsy is the most important method for AL Amyloidosis diagnosis in China. In addition, combined tests and some adjuvant methods played essential roles in the diagnosis. Further research is required to determine an acceptable and feasible diagnostic algorithm after symptom onset. INPLASY2022100096KEY MESSAGESThis scoping review details the characteristics and results of the recently published studies on diagnosing Amyloid light chain (AL) Amyloidosis in China.Biopsy is the most important method for AL Amyloidosis diagnosis in China.Combined tests and some adjuvant methods played essential roles in the diagnosis.
Topics: Humans; Adjuvants, Immunologic; Amyloidosis; East Asian People; Immunoglobulin Light-chain Amyloidosis
PubMed: 37387123
DOI: 10.1080/07853890.2023.2227425 -
Journal of Ethnopharmacology Dec 2023Compound Kushen (Sophora flavescens Aiton) Injection (CKI) is a Chinese herbal injection made from extracts of Kushen and Baituling (Heterosmilax japonica Kunth),... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Compound Kushen (Sophora flavescens Aiton) Injection (CKI) is a Chinese herbal injection made from extracts of Kushen and Baituling (Heterosmilax japonica Kunth), containing matrine (MAT), oxymatrine (OMT) and other alkaloids with significant anti-tumor activity, and is widely used as an adjuvant treatment for cancer in China.
AIM OF THE STUDY
The existing systematic reviews/meta-analyses (SRs/MAs) were re-evaluated to provide a reference for the clinical application of CKI.
MATERIALS AND METHODS
SRs/MAs of CKI adjuvant therapy for cancer-related diseases were searched in four English language databases: PubMed, Embase, Web of Science, and Cochrane Library, all from the time of database construction to October 2022. 5 researchers independently conducted literature search and identification according to the inclusion criteria, and the data of the final literature were independently extracted, and finally the AMSTAR 2 tool, PRISMA statement and GRADE classification were used to evaluate the methodological quality of the included SRs/MAs, the degree of completeness of reporting and the quality of evidence for outcome indicators. Database registration: PROSPERO ID:CRD42022361349.
RESULTS
Eighteen SRs/MAs were finally included, with studies covering non-small cell lung cancer, primary liver cancer, gastric cancer, colorectal cancer, breast cancer, head and neck tumors, and cancer-related bone pain. The evaluation showed that the methodological quality of the included literature was extremely low, but most of the literature reported relatively complete entries; nine clinical effectiveness indicators for non-small cell lung cancer and digestive system tumors were rated as moderate in the GRADE quality of evidence, and the quality of other outcomes was low to very low.
CONCLUSION
CKI is a potentially effective drug for the adjuvant treatment of neoplastic diseases and may be more convincing for the adjuvant treatment of non-small cell lung cancer and digestive system tumors; however, due to the low methodological and evidentiary quality of the current SRs, their effectiveness needs to be confirmed by more high-quality evidence-based medical evidence.
Topics: Humans; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drugs, Chinese Herbal; Lung Neoplasms; Systematic Reviews as Topic
PubMed: 37328082
DOI: 10.1016/j.jep.2023.116778 -
Neurotherapeutics : the Journal of the... Oct 2023N-Acetylcysteine (NAC) has shown promise as a putative neurotherapeutic for traumatic brain injury (TBI). Yet, many such promising compounds have limited ability to... (Review)
Review
N-Acetylcysteine (NAC) has shown promise as a putative neurotherapeutic for traumatic brain injury (TBI). Yet, many such promising compounds have limited ability to cross the blood-brain barrier (BBB), achieve therapeutic concentrations in brain, demonstrate target engagement, among other things, that have hampered successful translation. A pharmacologic strategy for overcoming poor BBB permeability and/or efflux out of the brain of organic acid-based, small molecule therapeutics such as NAC is co-administration with a targeted or nonselective membrane transporter inhibitor. Probenecid is a classic ATP-binding cassette and solute carrier inhibitor that blocks transport of organic acids, including NAC. Accordingly, combination therapy using probenecid as an adjuvant with NAC represents a logical neurotherapeutic strategy for treatment of TBI (and other CNS diseases). We have completed a proof-of-concept pilot study using this drug combination in children with severe TBI-the Pro-NAC Trial (ClinicalTrials.gov NCT01322009). In this review, we will discuss the background and rationale for combination therapy with probenecid and NAC in TBI, providing justification for further clinical investigation.
Topics: Child; Humans; Probenecid; Acetylcysteine; Pilot Projects; Brain Injuries, Traumatic; Brain; Blood-Brain Barrier
PubMed: 37596428
DOI: 10.1007/s13311-023-01422-z -
Cancers Dec 2023Despite recent advances, HER2-positive advanced breast cancer (ABC) remains a largely incurable disease, with resistance to conventional anti-HER2 drugs ultimately... (Review)
Review
Despite recent advances, HER2-positive advanced breast cancer (ABC) remains a largely incurable disease, with resistance to conventional anti-HER2 drugs ultimately unavoidable for all but a small minority of patients who achieve an enduring remission and possibly cure. Over the past two decades, significant advances in our understanding of the underlying molecular mechanisms of HER2-driven oncogenesis have translated into pharmaceutical advances, with the developing of increasingly sophisticated therapies directed against HER2. These include novel, more potent selective HER2 tyrosine kinase inhibitors (TKIs); new anti-HER2 antibody-drug conjugates; and dual epitope targeting antibodies, with more advanced pharmacological properties and higher affinity. With the introduction of adjuvant T-DM1 for incomplete responders to neoadjuvant therapy, fewer patients are relapsing, but for those who do relapse, disease that may be resistant to standard first- and second-line therapies requires new approaches. Furthermore, the risk of CNS relapse has not been abrogated by current (neo)adjuvant strategies; therefore, current research efforts are being directed towards this challenging site of metastatic disease. In this article, we review the currently available clinical data informing the effective management of HER2-positive breast cancer beyond standard first-line therapy with pertuzumab, trastuzumab, and taxanes, and the management of relapse in patients who have already been exposed to both these agents and T-DM1 for early breast cancer (EBC). We additionally discuss novel anti-HER2 targeted agents and combinations in clinical trials, which may be integrated into standard treatment paradigms in the future.
PubMed: 38201451
DOI: 10.3390/cancers16010023 -
ACS Nano Mar 2024Tapping into the innate immune system's power, nanovaccines can induce tumor-specific immune responses, which is a promising strategy in cancer immunotherapy. However,...
Tapping into the innate immune system's power, nanovaccines can induce tumor-specific immune responses, which is a promising strategy in cancer immunotherapy. However, traditional vaccine design, requiring simultaneous loading of antigens and adjuvants, is complex and poses challenges for mass production. Here, we developed a tumor nanovaccine platform that integrates adjuvant functions into the delivery vehicle, using branched polyguanidine (PolyGu) nanovaccines. These nanovaccines were produced by modifying polyethylenimine (PEI) with various guanidine groups, transforming PEI's cytotoxicity into innate immune activation. The PolyGu nanovaccines based on poly(phenyl biguanidine ) (Poly-PBG) effectively stimulated dendritic cells, promoted their maturation the TLR4 and NLRP3 pathways, and displayed robust immune activity. They significantly inhibited tumor growth and extended mouse survival. The PolyGu also showed promise for constructing more potent mRNA-based nanovaccines, offering a platform for personalized cancer vaccine. This work advances cancer immunotherapy toward potential clinical application by introducing a paradigm for developing self-adjuvanting nanovaccines.
Topics: Animals; Mice; Nanovaccines; Adjuvants, Immunologic; Immunotherapy; Cancer Vaccines; Neoplasms; Nanoparticles
PubMed: 38407021
DOI: 10.1021/acsnano.3c11637