An Engineered IgG-VHH Bispecific Antibody against SARS-CoV-2 and Its Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies are shown to be effective therapeutics for providing coronavirus disease 2019 (COVID-19) protection. However, recurrent variants arise and facilitate significant escape from current antibody therapeutics. Bispecific antibodies (bsAbs) represent a unique platform to increase antibody breadth and to reduce neutralization escape. Herein, a novel immunoglobulin G-variable domains of heavy-chain-only antibody (IgG-VHH) format bsAb derived from a potent human antibody R15-F7 and a humanized nanobody P14-F8-35 are rationally engineered. The resulting bsAb SYZJ001 efficiently neutralizes wild-type SARS-CoV-2 as well as the alpha, beta, gamma, and delta variants, with superior efficacy to its parental antibodies. Cryo-electron microscopy structural analysis reveals that R15-F7 and P14-F8-35 bind to nonoverlapping epitopes within the RBD and sterically hindered ACE2 receptor binding. Most importantly, SYZJ001 shows potent prophylactic and therapeutic efficacy against SARS-CoV-2 in three established mouse models. Collectively, the current results demonstrate that the novel bsAb format is feasible and effective, suggesting great potential as an inspiring antiviral strategy.

Radiomic analysis for predicting prognosis of colorectal cancer from preoperative 18F-FDG PET/CT.

BACKGROUND: To develop and validate a survival model with clinico-biological features and 18F- FDG PET/CT radiomic features via machine learning, and for predicting the prognosis from the primary tumor of colorectal cancer. METHODS: A total of 196 pathologically confirmed patients with colorectal cancer (stage I to stage IV) were included. Preoperative clinical factors, serum tumor markers, and PET/CT radiomic features were included for the recurrence-free survival analysis. For the modeling and validation, patients were randomly divided into the training (n = 137) and validation (n = 59) set, while the 78 stage III patients [training (n = 55), and validation (n = 23)] was divided for the further experiment. After selecting features by the log-rank test and variable-hunting methods, random survival forest (RSF) models were built on the training set to analyze the prognostic value of selected features. The performance of models was measured by C-index and was tested on the validation set with bootstrapping. Feature importance and the Pearson correlation were also analyzed. RESULTS: Radiomics signature (containing four PET/CT features and four clinical factors) achieved the best result for prognostic prediction of 196 patients (C-index 0.780, 95% CI 0.634-0.877). Moreover, four features (including two clinical features and two radiomics features) were selected for prognostic prediction of the 78 stage III patients (C-index was 0.820, 95% CI 0.676-0.900). K-M curves of both models significantly stratified low-risk and high-risk groups (P < 0.0001). Pearson correlation analysis demonstrated that selected radiomics features were correlated with tumor metabolic factors, such as SUVmean, SUVmax. CONCLUSION: This study presents integrated clinico-biological-radiological models that can accurately predict the prognosis in colorectal cancer using the preoperative 18F-FDG PET/CT radiomics in colorectal cancer. It is of potential value in assisting the management and decision making for precision treatment in colorectal cancer. Trial registration The retrospectively registered study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (No. 1909207-14-1910) and the data were analyzed anonymously.

The Improved Effects of a Multidisciplinary Team on the Survival of Breast Cancer Patients: Experiences from China.

This study aimed to explore whether different multidisciplinary team (MDT) organizations have different effects on the survival of breast cancer patients. A total of 16354 patients undergoing breast cancer surgery during the period 2006-2016 at the Fudan University Shanghai Cancer Center were retrospectively extracted. Patients treated by MDT were divided into a well-organized group and a disorganized group based on their organized MDT, professional attendance, style of data and information delivery, and the length of discussion time for each patient. Other patients, who were not treated by MDT, were placed in a non-MDT group as a comparator group. Each MDT patient was matched with a non-MDT patient, using propensity score matching to reduce selection bias. The Cox regression model was used to examine the difference in effects between groups. We found that the five-year survival rate of the well-organized MDT group was 15.6% higher than the non-MDT group. However, five-year survival rate of the disorganized MDT group was 19.9% lower than that of the non-MDT group. Patients in the well-organized MDT group had a longer survival time than patients in the non-MDT group (HR = 0.4), while the disorganized MDT group had a worse survival rate than the non-MDT group (HR = 2.8) based on the Cox model result. However, our findings indicate that a well-organized MDT may improve the survival rate of patients with breast cancer in China.

Performance of breast cancer screening methods and modality among Chinese women: a report from a society-based breast screening program (SBSP) in Shanghai.

To evaluate the screening performance of individual and combined use of clinical breast examination, ultrasonography and mammography in Chinese women, we conducted a biennial breast cancer screening program among 14,464 women aged 35 to 74 years old who lived in Qibao County, Minhang district of Shanghai, China, between May 2008 and Sept 2012. All participants were submitted to clinical breast examination, and then women with positive results and all women at age of 45-69 years old were preformed breast ultrasonography and mammography. The examination results were compared against pathological findings as the gold standard of reference. A total of 66 women were diagnosed with breast cancer in the two rounds of the screening, yielding an incident rate of 194 per 100,000 person-years. The sensitivity of clinical breast examination, ultrasonography and mammography alone were 61.4%, 53.7% and 67.3%, respectively. While mammography performed better in elder age groups and hormone receptor positive disease groups, ultrasonography had a higher sensitivity in younger age group and did not differ in sensitivity by estrogen receptor or progesterone receptor status. Combined use of the two imaging examinations increased the sensitivity in almost all age groups, but had a higher sensitivity in hormone receptor positive cancers than in those negative. Our results suggest that the Qibao modality is an effective strategy for breast cancer screening among Chinese women, especially for early detection of elder and hormone receptor positive breast cancer.