Identification Of Antigens Research Articles

Development and Application of a Fully Automated Chemiluminescence Enzyme Immunoassay for the Detection of Antibodies Against Porcine Circovirus 3 Cap

Porcine circovirus 3 (PCV3) is a small non-enveloped circovirus associated with porcine dermatitis and nephropathy syndrome (PDNS). It has occurred worldwide and poses a serious threat to the pig industry. However, there is no commercially available vaccine. PCV3 capsid protein (Cap) is an ideal antigen candidate for serodiagnosis. Here, a novel fully automated chemiluminescence enzyme immunoassay (CLEIA) was developed to detect antibodies (Abs) to Cap in porcine serum. Recombinant PCV3 Cap, self-assembled into virus-like particles (VLPs), was produced using baculovirus and coupled to magnetic particles (Cap-MPs) as carriers. Combined with an alkaline phosphatase (AP)–adamantane (AMPPD) system, Cap-Abs can be rapidly measured on a fully automated chemiluminescence analyzer. Under optimal conditions, a cut-off value of 31,508 was determined, with a diagnostic sensitivity of 96.8% and specificity of 97.3%. No cross-reactivity was observed with PCV1 and PCV2 and other common porcine pathogens, and both intra-assay and inter-assay coefficients were less than 5% and 10%, respectively. Prepared Cap-MPs can be stored at 4 °C for more than 6 months. Importantly, this CLEIA had a good agreement of 95.19% with the commercially available kit, demonstrating excellent analytical sensitivity and significantly reduced operating time and labor. A serological survey was then conducted, and showed that PCV3 continues to spread widely in South China. In conclusion, our CLEIA provides time and labor-saving, and a reliable tool for PCV3 epidemiological surveillance.

Practical SERS Substrates by Spray Coating of Silver Solutions for Deep Learning-Assisted Sensitive Antigen Identification

Surface-enhanced Raman spectroscopy (SERS) has long been recognized for its rapid and sensitive detection capabilities; however, challenges persist in practical fabrication of the substrates and interpreting complex data. Herein, we propose a deep learning (DL) assisted SERS approach to enable rapid and sensitive detection of analytes on a practical yet highly effective substrates prepared by direct spray-coating of a nanoparticle-free true solution of a reactive Ag ink and on-site thermal annealing mediated generation of nanostructures. This design ensured homogeneous distribution of Ag nanostructures throughout the entire substrate, significantly increasing the number of hotspots and enhancing the Raman signals, thereby achieving an impressive analytical enhancement factor of ~1010 in a reproducible and consistent manner. The diagnostic utility of this platform was demonstrated by detecting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein in both buffer and saliva, with detection limits of 74.3pg/mL and 7.43ng/mL, respectively. The DL-assisted SERS not only accurately identified the presence or absence of viral antigen, but also automatically quantified the viral load. This automatic identification achieved an outstanding accuracy of ~99.9%, highlighting the exceptional performance of the proposed platform. This simple, cost-effective, scalable, and ultra-sensitive DL-assisted SERS platform offers significant opportunities for early and precise detection in a range of analytical scenarios.

CD70: An Emerging Anticancer Target in Renal Cell Carcinoma and Beyond.

CD70 is an emerging target for anticancer therapies. It is an ideal antigen target given its limited expression in normal physiologic tissues and propensity to be aberrantly expressed in a variety of malignancies, thus limiting off-target toxicities. It is also heavily involved in immune homeostasis, and disruption of this pathway can help overcome tumor-related immune cell exhaustion. Recent phase I/II trials using cellular therapies targeting CD70, such as chimeric antigen receptor-T cells, have shown promising effectiveness and safety in treating relapsed or refractory renal cell carcinoma. Noncellular therapies targeting CD70, such as antibody-drug conjugates, monoclonal antibodies, radionuclides, and cytokines, are currently under investigation, with early data showing encouraging results as well. Efforts are already underway to further improve and optimize CD70-based therapies.

Plasmodium vivax antigen candidate prediction improves with the addition of Plasmodium falciparum data

Intensive malaria control and elimination efforts have led to substantial reductions in malaria incidence over the past two decades. However, the reduction in Plasmodium falciparum malaria cases has led to a species shift in some geographic areas, with P. vivax predominating in many areas outside of Africa. Despite its wide geographic distribution, P. vivax vaccine development has lagged far behind that for P. falciparum, in part due to the inability to cultivate P. vivax in vitro, hindering traditional approaches for antigen identification. In a prior study, we have used a positive-unlabeled random forest (PURF) machine learning approach to identify P. falciparum antigens based on features of known antigens for consideration in vaccine development efforts. Here we integrate systems data from P. falciparum (the better-studied species) to improve PURF models to predict potential P. vivax vaccine antigen candidates. We further show that inclusion of known antigens from the other species is critical for model performance, but the inclusion of only the unlabeled proteins from the other species can result in misdirection of the model toward predictors of species classification, rather than antigen identification. Beyond malaria, incorporating antigens from a closely related species may aid in vaccine development for emerging pathogens having few or no known antigens.

IMMU-34. PREDICTION OF TUMOR-ASSOCIATED ANTIGENS USING RADIOGENOMICS

Abstract INTRODUCTION Glioblastoma remains a disease with dismal prognosis. Immunotherapy demonstrated promising results against some refractory cancers. However, comparative results have not been accomplished in glioblastoma therapy due to lack of suitable tumor targets and considerable clonal heterogeneity. OBJECTIVE We propose leveraging radiogenomics using machine learning based on Pre-Op MRI to predict tumor antigen expression profiles displaying specific targets for immunotherapy. METHODS We collected RNAseq data and Pre-Op Axial T2-FLAIR images in 29 patients from IVY Glioblastoma Atlas Project. MRIs were segmented using LIFEx software as follows: 1) tumor + edema (T+E) and 2) whole brain (WB). The intended prediction was for tumor-associated antigens. H2O.ai software was used for prediction using an automated supervised machine learning algorithm. Antigens that achieved >55% area under the curve (i.e., prediction) were reanalyzed adjusting for reproducibility, time of analysis and maximum precision. RESULTS An average of 53.2 T2-FLAIR axial slices per patient were used for 3D reconstruction. We selected the following genes (ERBB2, TP53, IL10RA, CD163, EGFR and MGMT) for downstream analysis given their clinical, immunologic, and prognostic relevance. Regarding tumor-associated antigen prediction for ERBB2, TP53, IL10RA, CD163, EGFR and MGMT predicted 52%, 56%, 66%, 66%, 56% and 0%, on T+E segmentation respectively; The values were 49%, 93%, 87%, 47%, 37% and 0% for the respective WB group. Reanalysis revealed 100% prediction accuracy for the presence of mutant TP53 and IL10RA in both segmentation groups (T+E, WB). CD163 and EGFR prediction was 54% and 61% for the T+E group and 48% for both antigens in the WB group. CONCLUSION We successfully predicted the presence of two out of six antigens (i.e., mutant TP53 and IL10RA) in this patient cohort. Our approach can provide expeditious antigen identification to enable cellular therapy manufacturing for patients with unresectable newly diagnosed tumorsor those which relapsed geographically. Furthermore, this MRI-based methodology might provide a precision medicine approach to places that cannot afford costly testing (i.e., RNAseq).

Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment.

T cells have a critical role in mediating antitumour immunity. The success of immune checkpoint inhibitors (ICIs) for cancer treatment highlights how enhancing endogenous T cell responses can mediate tumour regression. However, mortality remains high for many cancers, especially in the metastatic setting. Based on advances in thegenetic characterization of tumours and identification of tumour-specific antigens, individualized therapeutic cancer vaccines targeting mutated tumour antigens (neoantigens) are being developed to generate tumour-specific T cells for improved therapeutic responses. Early clinical trials using individualized neoantigen vaccines for patients with advanced disease had limited clinical efficacy despite demonstrated induction of T cell responses. Therefore, enhancing T cell activity by improving the magnitude, quality and breadth of T cell responses following vaccination is one current goal for improving outcome against metastatic tumours. Another major consideration is how T cells can be further optimized to function within the tumour microenvironment (TME). In this Perspective, we focus on neoantigen vaccines and propose a new approach, termed Vax-Innate, in which vaccination through intravenous delivery or in combination with tumour-targeting immune modulators may improve antitumour efficacy by simultaneously increasing the magnitude, quality and breadth of T cells while transforming the TME into a largely immunostimulatory environment for T cells.

Overview on Immunopathology of Chronic Lymphocytic Leukemia and Tumor-Associated Antigens with Therapeutic Applications.

Chronic Lymphocytic Leukemia (CLL) is a clinically and biologically heterogeneous disease with a variable clinical course. The induction of a generalized state of immuno-suppression, leading to susceptibility to infections and the failure of anti-tumor immune responses, is a key feature of the clinical course of CLL. In addition to B-cell receptor (BCR) signaling in CLL, several receptor tyrosine kinases (RTKs) have been reported to be constitutively active in leukemic B cells, resulting in promoted survival and resistance to apoptosis induced by chemotherapy. Several treatment options are available for CLL, including a watch-and-wait strategy, chemotherapy, targeted therapies, immunotherapies such as adoptive cellular therapy (CAR T-Cell Therapy), stem cell transplantation (allogeneic transplantation), radiation therapy and surgery. The identification of Tumor-Associated Antigens (TAAs) is the bottleneck of tumor immunology and immunotherapy, serving as promising targets for precise diagnosis, monitoring, or therapeutic approaches. Numerous TAAs have been identified, and their application in immunotherapy holds promise for the treatment of CLL. Furthermore, extensive ongoing research aims to identify new cancer TAAs. In this review, our objective is to provide a comprehensive overview of CLL immunology and recent findings regarding advances in TAAs with therapeutic applications in CLL.

Optimisation of induction and purification protocols of recombinant 22.6kDa tegumental protein of Schistosoma spindale inprokaryotic vector

Schistosomosis is a prevalent zoonotic parasitic disease affecting both humans and animals on a global scale, with an estimated 165 million cattle and 200 million people impacted worldwide. Eventhough, serological methodologies designed for the identification of specific antibodies targeting parasitic antigens are esteemed for their high sensitivity, there are criticisms due to their incapacity to reliably indicate active infection, inability to correlate with the intensity of infection and lack of specificity. Enhancing the specificity of serological assays presents a significant challenge, primarily attributable to the identification and synthesis of specific antigens. In addressing these limitations, recombinant technology with specific immunogenic proteins as candidate antigens emerges as a viable alternative. In this study, induction of 22.6 kDa recombinant tegument protein of Schistosoma spindale was achieved using 0.6 mM concentration of IPTG at 37°C for four hours. Nickel chelating affinity chromatography was employed for protein purification, yielding maximum protein concentration at 75mM elution. Subsequently, the dialysis technique was employed to remove contaminants, while lyophilisation method was employed for protein concentration. The protein concentration post dialysis was measured at 0.220 mg/mL, while lyophilisation resulted in a concentration of 2mg/m Keywords: 22.6 kDa tegumental protein, Schistosoma spindale, dialysis, lyophilisation

Identification of immunogenic antigens and evaluation of vaccine candidates against Clostridium perfringens

Necrotic enteritis (NE) caused by Clostridium perfringens (C. perfringens) has resulted in significant losses for the poultry industry worldwide. Currently, there is no widely promoted vaccine for NE. In this study, immunoprecipitation (IP) was employed to isolate immunogenic proteins of C. perfringens, and 118 potential candidate antigens were identified through liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS). From these, three candidate antigen proteins were selected based on their predicted antigenicity, hydrophilicity, stability, and transmembrane signalling properties: ArcB (an ornithine aminotransferase), TmpC (a probable membrane lipoprotein), and EntB (a possible enterotoxin). These three proteins were successfully produced in large quantities using Escherichia coli (E. coli), with confirmed good solubility. Both in vitro and in vivo research demonstrated that these antigens possess strong immunogenicity, eliciting robust antigen-specific humoral and cellular immune responses in chickens and mitigating NE symptoms caused by C. perfringens. The candidate antigens identified through immunoproteomics hold potential as subunit vaccines against C. perfringens infection.

State of the Field: Cytotoxic Immune Cell Responses in C. neoformans and C. deneoformans Infection.

Cryptococcus neoformans is an environmental pathogen that causes life-threatening disease in immunocompromised persons. The majority of immunological studies have centered on CD4+ T-cell dysfunction and associated cytokine signaling pathways, optimization of phagocytic cell function against fungal cells, and identification of robust antigens for vaccine development. However, a growing body of literature exists regarding cytotoxic cells, specifically CD8+ T-cells, Natural Killer cells, gamma/delta T-cells, NK T-cells, and Cytotoxic CD4+ T-cells, and their role in the innate and adaptive immune response during C. neoformans and C. deneoformans infection. In this review, we (1) provide a comprehensive report of data gathered from mouse and human studies on cytotoxic cell function and phenotype, (2) discuss harmonious and conflicting results on cellular responses in mice models and human infection, (3) identify gaps of knowledge in the field ripe for exploration, and (4) highlight how innovative immunological tools could enhance the study of cytotoxic cells and their potential immunomodulation during cryptococcosis.

A comprehensive proteogenomic pipeline for neoantigen discovery to advance personalized cancer immunotherapy.

The accurate identification and prioritization of antigenic peptides is crucial for the development of personalized cancer immunotherapies. Publicly available pipelines to predict clinical neoantigens do not allow direct integration of mass spectrometry immunopeptidomics data, which can uncover antigenic peptides derived from various canonical and noncanonical sources. To address this, we present an end-to-end clinical proteogenomic pipeline, called NeoDisc, that combines state-of-the-art publicly available and in-house software for immunopeptidomics, genomics and transcriptomics with in silico tools for the identification, prediction and prioritization of tumor-specific and immunogenic antigens from multiple sources, including neoantigens, viral antigens, high-confidence tumor-specific antigens and tumor-specific noncanonical antigens. We demonstrate the superiority of NeoDisc in accurately prioritizing immunogenic neoantigens over recent prioritization pipelines. We showcase the various features offered by NeoDisc that enable both rule-based and machine-learning approaches for personalized antigen discovery and neoantigen cancer vaccine design. Additionally, we demonstrate how NeoDisc's multiomics integration identifies defects in the cellular antigen presentation machinery, which influence the heterogeneous tumor antigenic landscape.

Comparative analysis of the results of live anthrax vaccine identification by immunofluorescence and immunochromatography

INTRODUCTION. The quality evaluation of live anthrax vaccines will benefit from the implementation of alternative testing methods that are capable of specific identification of the Bacillus anthracis spore antigen using the appropriate diagnostic products that are authorised in the Russian Federation for the detection of B. anthracis spores.AIM. This study aimed to investigate the applicability of immunofluorescence analysis to the identification of live anthrax vaccines and compare this method with immunochromatography.MATERIALS AND METHODS. The study used commercial batches of a live anthrax vaccine and Russian diagnostic products, including diagnostic dry adsorbed fluorescent anti-anthrax spore immunoglobulins and an immunochromatographic assay (ICA) reagent kit for rapid detection and identification of B. anthracis spores (ICA system for B. anthracis). For smears and ICA system reactions, the authors prepared working solutions of bacterial suspensions at spore concentrations typical of the B. anthracis STI-1 vaccine strain. The spore concentrations were achieved using the pharmacopoeial reference standard (RS) for the opacity of bacterial suspensions of 10 international units (IU). Identification reactions involved the registration of immune complex formation.RESULTS. Immunofluorescence tests of the live anthrax vaccine demonstrated bright greenish-yellow envelope fluorescence with an intensity score of 3+ to 4+ for smears stained with diagnostic immunoglobulins at 1:32 and 1:64 dilutions. Immunochromatographic tests of the live anthrax vaccine detected the spore antigen at vaccine concentrations of 109 and 108 spores/mL, with the test strips showing two distinct dark-pink lines indicative of immunoprecipitation. According to the results obtained using the selected methods, the tested microbial culture was confirmed as B. anthracis.CONCLUSIONS. Immunochromatography and immunofluorescence tests with appropriate diagnostic preparations are convenient and reliable tools for the species-specific detection of B. anthracis STI-1 spores in the live anthrax vaccine. The results obtained in the anthrax vaccine identification tests provide a basis for recommending the above methods as supplementary alternatives to Ziehl–Neelsen bacteriological staining, which is currently prescribed by the State Pharmacopoeia of the Russian Federation.

Identification of feline erythrocyte antigen 6 and lack of alloimmunization to feline erythrocyte antigen 4 in cats.

New feline erythrocyte antigens (FEAs) have been described based on the presence of naturally occurring alloantibodies (NOAb), but their immunogenicity and clinical relevance are poorly understood. Describe the immunogenicity of FEA 4 after sensitizing FEA 4-negative cats lacking NOAb and characterize anti-FEA 4 alloantibodies produced, including their rate of appearance, agglutination titer, and immunoglobulin class. Nineteen healthy type A cats were blood typed for FEAs 1 to 5 to identify suitable donor-recipient pairs for FEA 4 sensitization. Four FEA 4-negative cats were transfused with FEA 4-positive red blood cells. Using a gel column technique, posttransfusion samples were screened daily for a week, weekly for a month, and monthly thereafter for anti-FEA 4 alloantibodies. Alloantibodies were not detected in the first 3 recipients despite repeated transfusions (1 and 3 additional transfusions for 2 and 1 recipients, respectively). In the 4th recipient, alloantibodies against its donor red blood cells were detected 21 days postsensitization. However, they were not directed against FEA 4, but rather against a novel FEA not yet described. The alloantibodies, named anti-FEA 6, remained detectable for >4 months after sensitization and were determined to be mostly immunoglobulin M based on sulfhydryl treatment. Feline erythrocyte antigen 4 does not appear to be immunogenic because repeated sensitization of 4 cats failed to produce detectable anti-FEA 4 alloantibodies. A new immunogenic antigen, named FEA 6, has been discovered, but additional studies are needed to document its clinical importance.

Structural Identification of Immunodominant Human Leukocyte Antigen (HLA) Epitopes Targeted by HLA-Specific Antibodies in Kidney Allograft Recipients

Structural Identification of Immunodominant Human Leukocyte Antigen (HLA) Epitopes Targeted by HLA-Specific Antibodies in Kidney Allograft Recipients

The role of kidney biopsy in the diagnosis of membranous nephropathy.

The discovery of the target antigen M-type phospholipase A2 receptor (PLA2R) with the possibility to detect anti-PLA2R antibodies in serum as well as the identification of several other antigens, overall accounting for almost all cases of membranous nephropathy, paved the way to a revolutionary change in the classification of membranous nephropathy. Serum anti-PLA2R autoantibody titers have been found to be highly specific diagnostic and prognostic biomarkers. Therefore, a positive test for anti-PLA2R serology in patients who present with nephrotic syndrome, normal kidney function, and no evidence of another process to account for proteinuria is believed to suffice to make a diagnosis of primary membranous nephropathy, thus removing the need for a renal biopsy. While technological advances will likely allow this proposal to prevail in the near future, the reasons why renal biopsy could still remain a critical tool for the management of membranous nephropathy in real life are discussed.

Finding potential targets in cell-based immunotherapy for handling the challenges of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hostile hematological malignancy under great danger of relapse and poor long-term survival rates, despite recent therapeutic advancements. To deal with this unfulfilled clinical necessity, innovative cell-based immunotherapies have surfaced as promising approaches to improve anti-tumor immunity and enhance patient outcomes. In this comprehensive review, we provide a detailed examination of the latest developments in cell-based immunotherapies for AML, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR)-engineered T-cell therapy, and natural killer (NK) cell-based therapies. We critically evaluate the unique mechanisms of action, current challenges, and evolving strategies to improve the efficacy and safety of these modalities. The review emphasizes how promising these cutting-edge immune-based strategies are in overcoming the inherent complexities and heterogeneity of AML. We discuss the identification of optimal target antigens, the importance of mitigating on-target/off-tumor toxicity, and the need to enhance the persistence and functionality of engineered immune effector cells. All things considered, this review offers a thorough overview of the rapidly evolving field of cell-based immunotherapy for AML, underscoring the significant progress made and the ongoing efforts to translate these innovative approaches into more effective and durable treatments for this devastating disease.

Deciphering avian hematopoietic stem cells by surface marker screening and gene expression profiling

BackgroundAvian species have played a pivotal role in developmental hematopoiesis research, leading to numerous critical discoveries. Avian influenza, particularly the H5N1 strain, poses a significant threat to poultry and has zoonotic potential for humans. Infections often result in abnormal hematologic profiles, highlighting the complex interplay between avian diseases and hematopoiesis. Many avian diseases can suppress immune cells in the bone marrow (BM), impacting immune responses. Studying hematopoietic stem cells (HSCs) in avian BM is crucial for understanding these processes and developing effective vaccines and protection strategies for both avian and human health. MethodsThis study adapted methods from mouse studies to isolate avian HSCs as Lineage-negative (Lin-) cells. These isolated cells were further identified as Lin-Sca1+c-Kit+ (LSK) and were found to be more prevalent than in control groups. RT-PCR analyses were conducted, showing that genes like MEIS1 and TSC1 were upregulated, while SIRT1, FOXO1, and AHR were downregulated in these stem cells. Screening for LSK markers revealed ten unique surface antigens in the Sca1+c-Kit+ cell populations, including highly enriched antigens such as CD178, CD227, and CD184. Additionally, studies on quail HSCs demonstrated that similar labeling techniques were effective in quail BM. ResultsThe research demonstrated that the identification of avian HSC-specific surface antigens provides valuable insights into the pathogenesis of avian influenza and other diseases, enhancing our understanding of how these diseases suppress HSC function. Notably, the upregulation of MEIS1 and TSC1 genes in LSK cells underscores their critical roles in regulating hematopoietic processes. Conversely, the downregulation of SIRT1, FOXO1, and AHR genes provides important clues about their roles in differentiation and immune response mechanisms. DiscussionThe findings of this study deepen our understanding of the effects of avian diseases on the immune system by identifying surface markers specific to avian HSCs. The suppression of HSC function by pathogens such as influenza highlights the importance of understanding these cells in developing targeted vaccines. These results represent a significant step towards improving global health security by mitigating risks associated with avian pathogens.

Preparation and Antigenic Site Identification of Monoclonal Antibodies against PB1 Protein of H9N2 Subtype AIV.

Recently, low pathogenic avian influenza virus (LPAIV), including H9N2 subtype, has been common clinical epidemic strains, and is widely distributed globally. The PB1 protein is a key component of the viral RNA polymerase complex (vRNP), and is vital to viral transcription and translation. In this study, to investigate the antigenic determinants in the PB1 protein, the truncated PB1 sequence (1bp-735bp) from H9N2 subtype AIV was amplified with PCR, and expressed in plasmid pET-28a (+). After purification, the recombinant PB1 protein was used to immunize BALB/c mice. Following immunization, hybridoma cells producing PB1-specific monoclonal antibodies were generated through the fusion of splenic lymphocytes with SP2/0 cells. Then, four stable hybridoma cell lines (5F12, 5B3, 2H9, and 3E6) were screened using indirect ELISA and Western blotting. Furthermore, two antigenic sites, 67NPIDGPLPED76 and 97ESHPGIFENS106, were identified through the construction of truncated overlapping fragments of the PB1 protein. These sites were conserved among 28 AIV strains, and were located on the PB1 protein surface. The findings offer a theoretical reference for the development and improvement of H9N2 vaccines and offer biological materials for virus detection during AIV infection mechanisms.

Expanding the repertoire of Antibody Drug Conjugate (ADC) targets with improved tumor selectivity and range of potent payloads through in-silico analysis.

Antibody-Drug Conjugates (ADCs) have emerged as a promising class of targeted cancer therapeutics. Further refinements are essential to unlock their full potential, which is currently limited by a lack of validated targets and payloads. Essential aspects of developing effective ADCs involve the identification of surface antigens, ideally distinguishing target tumor cells from healthy types, uniformly expressed, accompanied by a high potency payload capable of selective targeting. In this study, we integrated transcriptomics, proteomics, immunohistochemistry and cell surface membrane datasets from Human Protein Atlas, Xenabrowser and Gene Expression Omnibus utilizing Lantern Pharma's proprietary AI platform Response Algorithm for Drug positioning and Rescue (RADR®). We used this in combination with evidence based filtering to identify ADC targets with improved tumor selectivity. Our analysis identified a set of 82 targets and a total of 290 target indication combinations for effective tumor targeting. We evaluated the impact of tumor mutations on target expression levels by querying 416 genes in the TCGA mutation database against 22 tumor subtypes. Additionally, we assembled a catalog of compounds to identify potential payloads using the NCI-Developmental Therapeutics Program. Our payload mining strategy classified 729 compounds into three subclasses based on GI50 values spanning from pM to 10 nM range, in combination with sensitivity patterns across 9 different cancer indications. Our results identified a diverse range of both targets and payloads, that can serve to facilitate multiple choices for precise ADC targeting. We propose an initial approach to identify suitable target-indication-payload combinations, serving as a valuable starting point for development of future ADC candidates.

CAR T-cell therapy in meningioma: Current investigations, advancements and insight into future directions

Meningiomas, the most common tumors of the central nervous system (CNS), present significant challenges in treatment, particularly for atypical and anaplastic subtypes where standard therapies often fall short of therapeutic expectations. Chimeric Antigen Receptor (CAR) T-cell therapy, a groundbreaking immunotherapy approach, has demonstrated great success in hematological malignancies but faces obstacles in solid tumors, including CNS tumors like glioblastomas. This article provides a comprehensive review of the efficacy of CAR-T therapy in meningiomas, highlighting the tumor’s immunogenic potential and the challenges associated with applying this therapy in clinical practice. Through an extensive literature review, the study explores potential antigens for CAR-T targeting in meningiomas, shedding light on the tumor-immune microenvironment interactions. Challenges such as tumor heterogeneity, blood-brain barrier penetration, off-target effects, and tumor recurrence are discussed, alongside potential strategies to overcome these obstacles. The study also investigates recent advancements in CAR-T therapy, including the identification of novel target antigens and the development of engineering approaches to enhance therapeutic efficacy. Furthermore, the article highlights the importance of ongoing research efforts in exploring the tumor-immune dynamics in meningiomas and underscores the urgent need for clinical trials to validate the safety and efficacy of CAR-T therapy in this context. By addressing these challenges, CAR-T therapy holds the promise of revolutionizing meningioma treatment, offering new hope for patients suffering from this disease.