Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies\' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored for various tumor indications and some already approved for clinical use, challenges such as resistance due to factors like antigen expression, ADC processing, and payload have emerged. This review aims to outline the history of ADC development, their structure, mechanism of action, recent composition advancements, target selection, completed and ongoing clinical trials, resistance mechanisms, and intervention strategies. Additionally, it will delve into the potential of ADCs with novel markers, linkers, payloads, and innovative action mechanisms to enhance cancer treatment options. The evolution of ADCs has also led to the emergence of combination therapy as a new therapeutic approach to improve drug efficacy.

Acute myeloid leukaemia (AML) is a fatal and refractory haematologic cancer that primarily affects adults. It interferes with bone marrow cell proliferation. Patients have a 5 years survival rate of less than 30% despite the availability of several treatments, including chemotherapy, allogeneic haematopoietic stem cell transplantation (Allo-HSCT), and receptor antagonist drugs. Allo-HSCT is the mainstay of acute myeloid leukaemia treatment. Although it does work, there are severe side effects, such as graft-versus-host disease (GVHD). In recent years, chimeric antigen receptor (CAR)-T cell therapies have made significant progress in the treatment of cancer. These engineered T cells can locate and recognize tumour cells in vivo and release a large number of effectors through immune action to effectively kill tumour cells. CAR-T cells are among the most effective cancer treatments because of this property. CAR-T cells have demonstrated positive therapeutic results in the treatment of acute myeloid leukaemia, according to numerous clinical investigations. This review highlights recent progress in new targets for AML immunotherapy, and the limitations, and difficulties of CAR-T therapy for AML.

Antibody-drug conjugates (ADCs) represent a novel and promising approach in targeted therapy, uniting the specificity of antibodies that recognize specific antigens with payloads, all connected by the stable linker. These conjugates combine the best targeted and cytotoxic therapies, offering the killing effect of precisely targeting specific antigens and the potent cell-killing power of small molecule drugs. The targeted approach minimizes the off-target toxicities associated with the payloads and broadens the therapeutic window, enhancing the efficacy and safety profile of cancer treatments. Within precision oncology, ADCs have garnered significant attention as a cutting-edge research area and have been approved to treat a range of malignant tumors. Correspondingly, the issue of resistance to ADCs has gradually come to the fore. Any dysfunction in the steps leading to the ADCs\' action within tumor cells can lead to the development of resistance. A deeper understanding of resistance mechanisms may be crucial for developing novel ADCs and exploring combination therapy strategies, which could further enhance the clinical efficacy of ADCs in cancer treatment. This review outlines the brief historical development and mechanism of ADCs and discusses the impact of their key components on the activity of ADCs. Furthermore, it provides a detailed account of the application of ADCs with various target antigens in cancer therapy, the categorization of potential resistance mechanisms, and the current state of combination therapies. Looking forward, breakthroughs in overcoming technical barriers, selecting differentiated target antigens, and enhancing resistance management and combination therapy strategies will broaden the therapeutic indications for ADCs. These progresses are anticipated to advance cancer treatment and yield benefits for patients.

B7H3 is a co-stimulatory molecule for immune reactions found on the surface of tumor cells in a wide variety of tumors. Preclinical and clinical studies have reported it as a tumor target towards which various immunotherapy modalities could be directed. So far, good results have been obtained in hematological neoplasms; however, a contrasting situation is evident in solid tumors, including those of the CNS, which show high refractoriness to current treatments. The appearance of cellular immunotherapies has transformed oncology due to the reinforcement of the immune response that is compromised in people with cancer.
This article aims to review the literature to describe the advancement in knowledge on B7H3 as a target of CAR-T cells in pediatric gliomas to consider them as an alternative in the treatment of these patients.
Although B7H3 is considered a suitable candidate as a target agent for various immunotherapy techniques, there are still limitations in using CAR-T cells to achieve the desired success.
Results obtained with CAR-T cells can be further improved by the suggested proposals; therefore, more clinical trials are needed to study this new therapy in children with gliomas.

UNASSIGNED: Immunotherapy-based approaches are important breakthroughs with potential treatment benefits for melanoma patients. Mucin 1 (MUC1) is significantly upregulated in melanoma relative to normal cells. It has been reported that MUC1 influences cancer cell proliferation, apoptosis, invasion, and metastasis.The study aimed to explore the effect of MUC1 knockdown on the biological characteristics of the melanoma cell line B16F10 and evaluate whether MUC1 is an effective candidate target antigen for melanoma vaccine development.
UNASSIGNED: First, lentiviral vector-mediated short hairpin RNA (shRNA) was used to knockdown MUC1 in B16F10 cells (shMUC1-B16F10 cells). Next, we examined epithelial-mesenchymal transition (EMT), migration, proliferative capacity, clone formation, and distribution of cell cycle in shMUC1-B16F10 cells. Finally, the vaccine was prepared by repeated freeze-thawing of the shMUC1-B16F10 cells and used to subcutaneously immunize C57BL/6 mice, which were then challenged using B16F10 cells 10 days after the final vaccination.
UNASSIGNED: It was revealed that shMUC1 suppressed B16F10 proliferative and colony formation capacity, induced the arrest of cell cycle in the G0/G1 phase, and adjusted the expression of EMT-associated factors. MUC1 downregulation markedly suppressed the effect of B16F10 vaccine against melanoma in a mouse model. As compared with B16F10-vaccinated mice, B16F10-vaccinated mice in which MUC1 was silenced had reduced natural killer (NK) cytotoxicity, lower production of interferon-γ (IFN-γ), anti-MUC1 antibodies, perforin, granzyme B, and elevated tumor growth factor-β (TGF-β) level.
UNASSIGNED: MUC1 has strong melanoma vaccine immunogenicity, and induces the host\'s anti-tumor reaction. MUC1 knockdown inhibits the immune activity of B16F10 cell vaccine and anti-melanoma effect, suggesting the MUC1 is an important candidate target antigen of the melanoma vaccine.

Acute Myeloid Leukemia (AML) is an aggressive myeloid malignancy associated with high mortality rates (less than 30% 5-year survival). Despite advances in our understanding of the molecular mechanisms underpinning leukemogenesis, standard-of-care therapeutic approaches have not changed over the last couple of decades. Chimeric Antigen Receptor (CAR) T-cell therapy targeting CD19 has shown remarkable clinical outcomes for patients with acute lymphoblastic leukemia (ALL) and is now an FDA-approved therapy. Targeting of myeloid malignancies that are CD19-negative with this promising technology remains challenging largely due to lack of alternate target antigens, complex clonal heterogeneity, and the increased recognition of an immunosuppressive bone marrow. We carefully reviewed a comprehensive list of AML targets currently being used in both proof-of-concept pre-clinical and experimental clinical settings. We analyzed the expression profile of these molecules in leukemic as well normal tissues using reliable protein databases and data reported in the literature and we provide an updated overview of the current clinical trials with CAR T-cells in AML. Our study represents a state-of-art review of the field and serves as a potential guide for selecting known AML-associated targets for adoptive cellular therapies.

Historical standard of care treatments of T-cell malignancies generally entailed the use of cytotoxic and depleting approaches. These strategies are, however, poorly validated and record dismal long-term outcomes. More recently, the introduction and approval of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the therapy of B-cell malignancies. Translating this success to the T-cell compartment has so far proven hazardous, entangled by risks of fratricide, T-cell aplasia, and product contamination by malignant cells. Several strategies have been utilized to overcome these challenges. These include the targeting of a selective cognate antigen exclusive to T-cells or a subset of T-cells, disruption of target antigen expression on CAR-T constructs, use of safety switches, non-viral transduction, and the introduction of allogeneic compounds and gene editing technologies. We herein overview these historical challenges and revisit the opportunities provided as potential solutions. An in-depth understanding of the tumor microenvironment is required to optimally harness the potential of the immune system to treat T-cell malignancies.

In this study, we conducted a meta-analysis (MA) and systematic review to evaluate the effectiveness of vaccines against post-weaning diarrhea (PWD), caused by enterotoxigenic Escherichia coli (ETEC), in piglets. A Bayesian network meta-analysis (NMA) was also performed to compare the effects of combining different target antigens on vaccine efficacy. Relevant electronic databases were searched using pre-specified search terms, and 17 studies were selected based on three outcomes: diarrhea, mortality, and average daily weight gain (ADWG). In pairwise MA, the vaccinated group showed a significant decrease in diarrhea (OR = 0.124 [0.056, 0.275]) and mortality (OR = 0.273 [0.165, 0.451]), and a significant increase in ADWG (SMD = 0.699 [0.107, 1.290]) compared with those in controls. Furthermore, NMA results showed that all vaccine groups, except for group D (LT enterotoxin), were effective against PWD. Rank probabilities indicated that the F4 + F18 + LT combination was the best regimen for preventing diarrhea (SUCRA score = 0.92) and mortality (SUCRA score = 0.89). NMA also demonstrated that, among the vaccine groups, those inducing simultaneous anti-adhesion and antitoxin immunity had the highest efficacy. Our results provide evidence-based information on the efficacy of vaccines in reducing PWD incidence in pigs and may serve as guidelines for antigen selection for commercial vaccine development in the future.

BACKGROUND: Breast cancer (BC) is a highly prevalent solid cancer with a high-rise infiltration of immune cells, turning it into a significant candidate for tumor-specific immunotherapies. Chimeric antigen receptor (CAR)-T cells are emerging as immunotherapeutic tools with genetically engineered receptors to efficiently recognize and attack tumor cells that express specific target antigens. Technological advancements in CAR design have provided five generations of CAR-T cells applicable to a wide range of cancer patients while boosting CAR-T cell therapy safety. However, CAR-T cell therapy is ineffective against breast cancer because of the loss of specified antigens, the immunosuppressive nature of the tumor and CAR-T cell-induced toxicities. Next-generation CAR-T cells actively pass through the tumor vascular barriers, persist for extended periods and disrupt the tumor microenvironment (TME) to block immune escape.
CONCLUSIONS: CAR-T cell therapy embodies advanced immunotherapy for BC, but further pre-clinical and clinical assessments are recommended to achieve maximized efficiency and safety.

There have been only several studies on the correlation between glomerular exostosin expression and membranous lupus nephritis. In this study, we validate the previous findings in Chinese patients with class 5 lupus nephritis.
One hundred sixty-five patients with class 5 lupus nephritis and varying numbers of control patients were included. Exostosin1/exostosin2 staining was performed by immunohistochemistry, and the staining intensity was quantified using an imaging analysis system. Between-group comparisons were tested for statistical significance using the Pearson chi-squared test, the Fisher exact test, the unpaired t test, the Mann-Whitney U test, or one-way ANOVA.
In total, 46% of patients with class 5 lupus nephritis, 9% of patients with class 5 + 3/4 lupus nephritis, and none of the other classes of lupus nephritis were exostosin positive. Only three patients were exostosin positive among the 61 patients with other secondary membranous nephropathy. The exostosin-positive rate in nephrotic patients was significantly higher than that in patients without nephrotic syndrome (P<0.001), and the exostosin staining intensities of the patients with exostosin-positive class 5 were positively correlated with proteinuria (r=0.53; P<0.001). Compared with the patients with exostosin-negative cases, the patients with exostosin-positive cases had higher proteinuria levels (3.9 [interquartile range, 2.0-6.3] g/d versus 2.3 [interquartile range, 1.0-3.6] g/d; P<0.001); lower scores of activity index (1 [interquartile range, 1-2] versus 2 [interquartile range, 1-3]; P=0.001), chronicity index (1 [interquartile range, 0-2] versus 2 [interquartile range, 1-2]; P=0.02), and tubular atrophy score (0 [interquartile range, 0-1] versus 1 [interquartile range, 0-1]; P=0.008); a higher proportion of extensive subepithelial deposition (62% versus 27%; P<0.001); a similar treatment response; and comparable time to kidney end point. Among the 47 patients with class 5 who underwent repeat biopsy, 97% of those with exostosin-negative cases remained negative, whereas 44% of those with exostosin-positive cases were still positive. The rate of histologic transition in the patients with exostosin-negative class 5 was significantly higher than that in the patients with exostosin-positive class 5 (59% versus 22%; P=0.03).
Exostosin positivity occurred frequently in patients with class 5 lupus nephritis, and patients with exostosin-positive cases had more severe proteinuria and a lower rate of histologic transition than the exostosin-negative patients.