Alveolar echinococcosis (AE), caused by the larval stage of the tapeworm Echinococcus multilocularis, is a serious parasitic disease that presents significant health risks and challenges for both patients and healthcare systems. Accurate and timely diagnosis is essential for effective management and improved patient outcomes. This review summarizes the latest diagnostic methods for AE, focusing on serological tests and imaging techniques such as ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). Each imaging modality has its strengths and limitations in detecting and characterizing AE lesions, such as their location, size, and invasiveness. US is often the first-line method due to its non-invasiveness and cost-effectiveness, but it may have limitations in assessing complex lesions. CT provides detailed anatomical information and is particularly useful for assessing bone involvement and calcification. MRI, with its excellent soft tissue contrast, is superior for delineating the extent of AE lesions and their relationship to adjacent structures. PET/CT combines functional and morphological imaging to provide insights into the metabolic activity of lesions, which is valuable for monitoring treatment response and detecting recurrence. Overall, this review emphasizes the importance of a multifaceted diagnostic approach that combines serological and imaging techniques for accurate and early AE diagnosis, which is crucial for effective management and improved patient outcomes.

Background. Th2 cytokines (e.g. IL-4, IL-5, IL13) drive defined allergic reactions and various autoimmune and inflammatory diseases including atopic dermatitis (AD), asthma and rhinitis. IL-4Ra is a receptor shared by both IL-4 and IL-13, thus blocking of IL-4Ra could prevent both IL-4 or IL-13 mediated Th2 inflammatory response. Dupilumab (Dupixent) is a humanized anti-IL-4Ra monoclonal antibody which binds to human IL-4Ra and attenuates IL-4/IL-13 mediated Th2 inflammation. It has been approved for treating moderate to severe AD and asthma. However, since Dupilumab isn’t cross-reacting to mouse IL-4Ra, there is an unmet need for a robust mouse model to evaluate Dupilumab biosimilars at preclinical stages. In this study, we described an oxazolone induced AD model in hIL-4/hIL-4Ra double knock-in mice and its application to evaluate Dupilumab and its biosimilars. Methods. The oxazolone induce AD mouse model was established in hIL-4/hIL-4Ra double knock-in mice by repeated topical applications of Oxazolone on ears. Oxazolone-induced mice received subcutaneous injection of Dupilumab at 25 mg/kg or 50 mg/kg. Dermatitis activity was assessed by measuring ear thickness, ear skin erosion, redness and scaling every other day. Serum were collected at the study end and IgE levels were measured by ELISA. In addition, spleens were also collected and their weights were compared. Ear were collected at study end and proceeded with cytokine analysis and pathology evaluation. Results. Repeated topical application of oxazolone on mouse ears induced AD-like phenotypes including ear skin swelling, erythema and scaling, drastic elevation of IgE in serum, excessive production of human IL-4 cytokine as well as excessive inflammatory cell infiltration in ear skin, which suggests oxazolone is able to induce AD in this hIL-4/hIL-4Ra double knock-in mice. Subcutaneous injection of Dupilumab at two different doses levels, 25 mg/kg and 50 mg/kg successfully ameliorated ear skin swelling, erythema and scaling at the study end. In addition, Dupilumab at both dose levels significantly reduced the IgE level in serum and mitigated the inflammatory cell infiltration, e.g. eosinophil infiltration, in mouse ear. Furthermore, Dupilumab treatment significantly reduced mouse IL-6 and mouse KC/GRO levels in mouse ear. However, Dupilumab at both dose levels did not change the serum levels of human IL-4 as well as some other Th1 cytokines such as IFN-γ, IL-1β, TNF-α, etc. in mouse ear. Conclusion. In summary, repeated challenge with Oxazolone in hIL-4/hIL-4Ra double knock-in mice resulted in the development of AD with a Th2-like hypersensitivity, mimicking the key features and pathology of the human disease, which responded to standard of care treatment Dupilumab. This provides a valuable translational model for the evaluation of future biosimilars of Dupilumab. Citation Format: Tao Yang, Rongfei Lu, Xiaofei Xu, Likun Zhang, Dawei Wang, Xinhe Feng, Xiaoyu An, Jessie (Jingjing) Wang, Xianfei He, Carl K. Edwards. Oxazolone induced atopic dermatitis mouse model using hIL-4/hIL-4Ra double knock-in mice, a preclinical mouse model for evaluating Dupilumab biosimilars. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5133.

Cancer immunotherapy remains limited by insufficient antigen presentation and immunosuppressive tumor microenvironment. Here, we present a vaccine strategy based on cold atmospheric plasma (CAP)–engineered tumor cell–derived immune reprogramming nanovesicles (CAPTURE) that integrates spatiotemporal sequential immunization to potentiate antitumor immunity. CAPTURE is engineered from tumor cells pretreated with CAP, which up-regulates major histocompatibility complex class I expression via p62-mediated autophagy to promote full-spectrum epitope antigen presentation, and surface-functionalized anti-CD28 (αCD28) on CAPTURE provides costimulatory signals to directly activate T cells through αCD28-CD28, bypassing B7-CTLA-4–mediated T cell inhibition. Under spatiotemporal sequential immunity, CAPTURE exhibits homologous tumor targeting and lymph node accumulation, enhancing antigen presentation for CD8 ⁺ T cell activation and tumor immunogenic remodeling. In mouse models, CAPTURE achieved near-complete tumor suppression, driven by amplified cytotoxic T cell responses, increased T cell clonal diversity, and CXCR3-mediated tumor infiltration. This study presents a universal biomimetic nanovaccine strategy that can reshape both T cells’ immunity and tumor cells’ immunogenicity, induce broad-spectrum immune responses to overcome immune evasion, and offer unique insights and innovative technologies for precision cancer immunotherapy.

Background. Immune checkpoint molecules are essential for modulating immune responses and maintaining self-tolerance. While immune checkpoint inhibitors have improved the treatment of a broad spectrum of cancers, many of them are also believed to play a critical role in the induction of immune related adverse events (irAEs) such as autoimmune and inflammatory diseases. For example, patients receiving anti-PD-1 based therapy frequently develop colitis. In addition, dysfunctional PD-1 signalling has also been linked to increasing susceptibility to autoimmune and inflammatory diseases. Therefore, immune checkpoint molecule agonist which could, like their natural ligands, confer a great potential in suppressing excessively activated immune response observed in autoimmune and inflammatory diseases. Methods. In the first part, the proinflammation effects of a Pembrolizumab analogue was evaluated in a MC38-OVA colorectal tumor bearing mice treated with or without DSS. In the second part, an anti-hPD-1 agonistic antibody at 10 mg/kg was evaluated in acute DSS IBD model. Results. In the MC38-OVA colorectal cancer model, mice treated with Pembrolizumab analogue only or Pembrolizumab analogue plus 1.5% DSS showed significant tumor growth inhibition (100% TGI and 92.01% TGI, respectively at Day 27) compared to their respective control group, which suggests this Pembrolizumab analogue induced robust anti-tumor immunity against MC38-OVA tumors. Notably, 8/8 mice treated with Pembrolizumab analogue only showed complete tumor regression, while only 5/8 mice treated with Pembrolizumab analogue plus DSS showed complete tumor regression. Taken together, these results suggest DSS treatment leading to a proinflammatory context could compromise anti-hPD-1 anti-tumor efficacy. Moreover, mice treated with Pembrolizumab analogue plus DSS also showed 3.59% more Body Weight Loss (BWL) in comparison to 1.5% DSS only group, suggesting that Pembrolizumab analogue could exacerbate DSS induced colitis. In the acute DSS IBD model, mice treated with an agonistic anti-hPD-1 antibody showed significantly lower disease score (DAI 5.3 vs DAI 2.4) and less BWL (BWL 13.44% vs BWL 3.31%) in comparison to isotype control group. In addition, pathology results showed that mice treated with agonistic anti-hPD-1 exhibits significantly less inflammatory cell infiltration and colonic lesions when compared to isotype control group. Conclusion. In summary, we reported in this study that blocking of PD-L1/PD-1 signalling axis by a PD-1 antagonist activated T cell function which at the same time aggravated DSS induced colitis in mouse. In contrast, activation of PD-L1/PD-1 signalling pathway by a PD-1 agonist alleviated DSS induced colitis. Citation Format: Tao Yang, Rongfei Lu, kaixia lian, Likun Zhang, Dawei Wang, Xinhe Feng, Xiaoyu An, Jessie (Jingjing) Wang, Carl K. Edwards. PD-1/PD-L1 signalling axis, “a double-edged sword” in DSS induced colitis mouse model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5134.