The global pandemic of COVID-19 poses a huge threat to the health and lives of people all over the world, and brings unprecedented pressure to the medical system. We need to establish a practical method to improve the efficiency of treatment and optimize the allocation of medical resources. Due to the influx of a large number of patients into the hospital and the running of medical resources, blood routine test became the only possible check while COVID-19 patients first go to a fever clinic in a community hospital. This study aims to establish an efficient method to identify key indicators from initial blood routine test results for COVID-19 severity prediction. We determined that age is a key indicator for severity predicting of COVID-19, with an accuracy of 0.77 and an AUC of 0.92. In order to improve the accuracy of prediction, we proposed a Multi Criteria Decision Making (MCDM) algorithm, which combines the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) and Naïve Bayes (NB) classifier, to further select effective indicators from patients’ initial blood test results. The MCDM algorithm selected 3 dominant feature subsets: {Age, WBC, LYMC, NEUT} with a selection rate of 44%, {Age, NEUT, LYMC} with a selection rate of 38%, and {Age, WBC, LYMC} with a selection rate of 9%. Using these feature subsets, the optimized prediction model could achieve an accuracy of 0.82 and an AUC of 0.93. These results indicated that Age, WBC, LYMC, NEUT were the key factors for COVID-19 severity prediction. Using age and the indicators selected by the MCDM algorithm from initial blood routine test results can effectively predict the severity of COVID-19. Our research could not only help medical workers identify patients with severe COVID-19 at an early stage, but also help doctors understand the pathogenesis of COVID-19 through key indicators.

Targeting cancer antigens by T cell-engaging bispecific antibody (BiAb) or chimeric antigen receptor T cell therapy has achieved successes in hematological cancers, but attempts to use it to fight solid cancers have been disappointing, in part due to antigen escape. MEK inhibitor had limited activity as a single agent, but enhanced antitumor activity when combined with other therapies, such as targeted drugs or immunotherapy agents. This study aimed to analyze the expression of B7-H3 in non-small-cell lung cancer (NSCLC) and bladder cancer (BC) and to evaluate the combinatorial antitumor effect of B7-H3 × CD3 BiAb with MEK inhibitor trametinib. We found B7-H3 was highly expressed in NSCLC and BC compared with normal samples and its increased expression was associated with poor prognosis. Treatment with trametinib alone could induce apoptosis in tumor cell, while has no effect on T cell proliferation, and a noticeable elevation of B7-H3 expression in tumor cells was also observed following treatment. B7-H3 × CD3 BiAb specifically and efficiently redirected their cytotoxicity against B7-H3 overexpressing tumor cells both in vitro and in xenograft mouse models. While trametinib treatment alone affected tumor growth, the combined therapy increased T cell infiltration and significantly suppressed tumor growth. Together, these data suggest that combination therapy with B7-H3 × CD3 BiAb and MEK inhibitor may serve as a new therapeutic strategy in the future clinical practice for the treatment of NSCLC and BC.

The therapeutic use of bispecific T‐cell engaging (BiTE) antibodies has shown great potential for treating malignancies. BiTE can simultaneously engage CD3ε on T cells and tumor antigen on cancer cells, thus exerting an effective antitumor effect. Nevertheless, challenges in production, manufacturing, and short serum half‐life of BiTE have dampened some of the promise and impeded the pace of BiTE‐based therapeutics to combat diseases. Nowadays, in vitro‐transcribed mRNA has achieved programmed production, which is more flexible and cost‐effective than the traditional method of producing recombinant antibody. Here, the authors have developed a BiTE‐based mRNA treatment by encapsulating mRNA encoding B7H3×CD3 BiTE into a novel ionizable lipid nanoparticles (LNPs). The authors have found that LNPs have high transfection efficiency, and the hepatosplenic targeting capability of produce high concentrations of BiTE. Above all, a single intravenous injection of BiTE mRNA‐LNPs could achieve high levels of protein expression in vivo and significantly prolonged the half‐life of the BiTE, which can elicit robust and durable antitumor efficacy against hematologic malignancies and melanoma. Therefore, their results suggested that the therapeutic strategy based on mRNA expression of B7H3×CD3 BiTE is of potential research value and has promising clinical application prospects.

Rationale: Current traditional treatment options are frequently ineffective to fight against ovarian cancer due to late diagnosis and high recurrence. Therefore, there is a vital need for the development of novel therapeutic agents. B7H3, an immune checkpoint protein, is highly expressed in various cancers, representing it a promising target for cancer immunotherapy. Although targeting B7H3 by bispecific T cell-engaging antibodies (BiTE) has achieved successes in hematological malignancies during recent years, attempts to use them for the treatment of solid cancers are less favorable, in part due to the heterogeneity of tumors. Sorafenib is an unselective inhibitor of multiple kinases currently being tested in clinical trials for several tumors, including ovarian cancer which showed limited activity and inevitable side effect for ovarian cancer treatment. However, it is able to enhance antitumor immune response, which indicates sorafenib may improve the efficiency of immunotherapy. Methods: We evaluated the expression of B7H3 in ovarian cancer using online database and validated its expression of tumor tissues by immunohistochemistry staining. Then, B7H3 expression and the effects of sorafenib on ovarian cancer cell lines were determined by flow cytometry. In addition, 2D and 3D ovarian cancer models were established to test the combined therapeutic effect in vitro . Finally, the efficiency of B7H3×CD3 BiTE alone and its combination with sorafenib were evaluated both in vitro and in vivo . Results: Our data showed that B7H3 was highly expressed in ovarian cancer compared with normal samples. Treatment with sorafenib inhibited ovarian cancer cell proliferation and induced a noticeable upregulation of B7H3 expression level. Further study suggested that B7H3×CD3 BiTE was effective in mediating T cell killing to cancer cells. Combined treatment of sorafenib and B7H3×CD3 BiTE had synergistic anti-tumor effects in ovarian cancer models. Conclusions: Overall, our study indicates that combination therapy with sorafenib and B7H3×CD3 BiTE may be a new therapeutic option for the further study of preclinical treatment of OC.

Background Targeting cancer antigens by T cell-engaging bispecific antibody (BiAb) or chimeric antigen receptor T cell therapy has achieved successes in haematological cancers, but attempts to use them to fight solid cancers have been disappointing, in part due to antigen escape. MEK inhibitor had limited activity as a single agent, but enhanced antitumor activity when combined with other therapies, such as targeted drugs or immunotherapy agents. This study aimed to analyze the expression of B7-H3 in non-small-cell lung cancer (NSCLC) and bladder cancer (BC) and to evaluate the combinatorial antitumor effect of a B7-H3 × CD3 BiAb with MEK inhibitor trametinib. Methods We analyzed the mRNA expression of B7-H3 in NCSLC and BC using Oncomine database and validated its expression by immunohistochemistry staining of clinical samples. B7-H3 expression and the effects of trametinib on RAS-mutated NSCLC and BC cell lines were determined by flow cytometry. Antitumor efficacy of B7-H3 × CD3 BiAb alone and its combination with trametinib were evaluated both in vitro and in vivo. Results B7-H3 was highly expressed in NSCLC and BC compared with normal samples and its increased expression was associated with poor prognosis. Treatment with trametinib alone could induce apoptosis in tumor cell, while has no effect on T cell proliferation, and a noticeable elevation of B7-H3 expression in tumor cells was also observed following treatment. B7-H3 × CD3 BiAb specifically and efficiently redirected their cytotoxicity against B7-H3-overexpressing tumor cells both in vitro and in xenograft mouse models, which was synergized by trametinib. While trametinib treatment alone affected tumor growth, the combined therapy increased T cell infiltration and significantly suppressed tumor growth. Conclusion Together, these data suggest that combination therapy with B7-H3 × CD3 BiAb and MEK inhibitor may serve as a new therapeutic strategy in the future clinical practice for the treatment of NSCLC and BC.