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Bennett Tochukwu Amaechi,1 Sahar Mohseni,1 Andrew M Dillow,1 Mackenzie H Cvelich,2 Ana Stevanovic,3 Alphonsus Igoche Abah,1 Fatemeh Movaghari Pour,1 Rayane Farah,1 Yuko Kataoka,1 Maria Camila Restrepo,1 Dennis Zhang,4 Leonora Ethleen Leigh,4 Joel Basilan4 1Department of Comprehensive Dentistry, University of Texas Health San Antonio, San Antonio, TX, USA; 2Department of Developmental Dentistry, University of Texas Health San Antonio, San Antonio, TX, USA; 3Kleberg Advanced Microscopy Center, University of Texas at San Antonio, San Antonio, TX, USA; 4Research & Development – Oral Care, BASF Corporation, Tarrytown, NY, USACorrespondence: Bennett Tochukwu Amaechi, Department of Comprehensive Dentistry, School of Dentistry, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA, Tel +1 210 567 3185, Email amaechi@uthscsa.eduPurpose: Erosive tooth wear (ETW) is characterized by subsurface demineralization and tooth substance loss with crater formation. Remineralization of subsurface demineralization has previously been demonstrated; however, repair of the eroded surface is still under investigation. This study investigated the effectiveness of mouthwashes containing hydrolyzed wheat protein (HWP) in repairing ETW through promotion of organized crystal growth.Methods: Enamel Erosion was created on 210 enamel blocks by 10-minute demineralization in 1% Citric Acid (pH 3.5). Then, blocks were randomly assigned to seven groups (30/group); (A) 0.2% HWP, B) 1% HWP, (C) 2% HWP, (D) 1% HWP + 0.05% NaF, (E) Listerine™ mouthwash, (F) 0.02% NaF Crest™ Pro-health mouthwash and (G) artificial saliva (AS) only. Groups were subjected to daily pH-cycling consisting of one 5-minute erosive challenge with citric acid, three 1-minute mouthwash treatment periods, and then storage in AS for the rest of the time for 28 days. Treatment effects were assessed using SEM-EDX. Statistical analysis was by ANOVA and Tukey’s multiple comparison.Results: In groups exposed to HWP-containing mouthwashes, there was growth of fiber-like crystals that increased in packing density in a dose-dependent manner (0.2%, 1%, 2%) on the eroded enamel surfaces, with increased calcium and phosphate contents on the treated surfaces. The non-HWP-containing groups had the eroded surfaces covered by structureless deposit layer firmly attached to the surface.Conclusion: Treating eroded enamel surface with HWP-containing mouthwash resulted in repair of the damaged tissue by formation of a protective layer of crystal deposits within and on the eroded enamel tissue.Keywords: hydrolyzed wheat protein, Enameguard, erosive tooth wear, acid erosion, erosion repair, remineralization

Objectives To investigate the effects of radiofrequency (RF) energy, applied through a power toothbrush, on the structural morphology of dental plaque and its bacteria components. Previous studies showed that a toothbrush powered by RF (ToothWave) effectively reduces extrinsic tooth stains, plaque, and calculus. However, the mechanism by which it reduces dental plaque deposits is not fully established. Materials and Methods Multispecies plaques at sampling time points of 24, 48, and 72 hours were treated with the application of RF using ToothWave with the toothbrush bristles 1 mm above the plaque surface. Groups that underwent the same protocol but without RF treatment served as paired controls. Confocal laser scanning microscope (CLSM) was used to determine cell viability at each time point. Plaque morphology and bacteria ultrastructure were viewed using scanning electron microscope (SEM) and transmission electron microscope (TEM), respectively. Statistical Analysis Data were analyzed statistically using analysis of variance (ANOVA) and Bonferroni post-tests. Results At each time, RF treatment significantly (p Conclusion The application of RF via a power toothbrush can disrupt plaque morphology and kill bacteria. These effects were enhanced by the combined application of RF and toothpaste.

Obesity and related co-morbidities lead to a decrease in health-related quality of life (HRQOL) and mood. Lifestyle strategies may improve these outcomes. However, the efficacy of exercise in conjunction with a weight-loss diet on HRQOL and mood is unclear. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to examine whether the addition of exercise to energy-restricted dietary programs improves HRQOL and mood status when compared with energy-restricted diets alone in overweight and obese adults.Eligible RCTs were identified by searching PubMed/MEDLINE, EMBASE, ISI (Web of sciences), Scopus, and Google Scholar up to April 2021. Summary effects were derived using a random-effects model. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.The meta-analysis revealed that an energy-restricted diet plus exercise compared with an energy-restricted diet alone had no significant effects on depression (n = 6, hedges'g = - 0.04, 95% CI: - 0.28,0.20), MOS 36-Item Short-Form Health Survey (SF-36)-physical component summary scores (n = 8, weighted mean difference (WMD) = 1.51, 95% CI: - 0.16, 3.18), SF36-mental component summary scores (n = 7, WMD = 0.64, 95% CI: - 1.00, 2.28), and HRQOL disease-specific questionnaire scores (n = 5, hedges'g = 0.16, 95% CI: - 0.09, 0.40). The GRADE revealed that the quality of evidence was low for disease-specific HRQOL scores, and depression status; and high for physical and mental health assessed by SF-36.In our sample of overweight and obese adults, no beneficial effect of adding exercise to an energy-restricted diet was found in terms of HRQOL and Depression.

Background and Purpose: Invasive candidiasis is a life-threatening condition that kills a large number of immunocompromised patients each year worldwide. We used postantifungal effect studies to analyze the activities of anidulafungin (AFG), as a clinically crucial antifungal drug, amphotericin B (AMB), and fluconazole (alone and in combinations) against FLC-susceptible and -resistant Candida albicans (C. albicans) isolates obtained from the cancer patients. Materials and Methods: We tested the phenomenon of post antifungal effects of FLC, AMB, AFG, and combinations of FLC+AFG, AFG+AMB, and FLC+AMB against 17 C. albicans isolates obtained from the oral cavity of cancer patients. Isolates that had not been exposed to antifungals, served as a control group. Colony counts were performed at 0, 2, 4, 6, and 24 h after a brief (1 h) exposure to antifungal. Results: The FLC had no detectable post-antifungal effect independent of antifungal concentration and resembled drug-free FLC (control). Significant variations in the postantifungal effect were observed when all AMB and AFG were compared to FLC. The combination of AFG and AMB with FLC resulted in effective activity compared to FLC alone. Combination regimens were rated as indifferent in general. Interestingly, low dosages of the AFG displayed increasing fungistatic action as it approached a fungistatic endpoint against C. albicans isolates (n=17). Conclusion: Our findings suggested that brief exposure to AFG, in combination with FLC and AMB, at low concentrations of the medicines utilized, could be effective in the evaluation and optimization of new dosage regimens to manage candidiasis. However, future studies will determine the clinical utility of our findings.

This systematic review and meta-analysis of controlled clinical trials was performed to evaluate the effects of weight-loss diets plus exercise compared with weight-loss diets alone on inflammatory biomarkers in adults. PubMed, Scopus, EMBASE, Web of Science (ISI), and Google Scholar were searched up to April 2021. Overall effects were derived using a random effects model. The overall quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty-nine trials were included in this systematic review and meta-analysis. The meta-analysis showed no significant difference in serum high sensitivity C-reactive protein (hs-CRP) [weighted mean difference (WMD) = ���0.004 mg/l, 95% CI: ���0.140, 0.132, P = 0.954], interleukin-6 (IL-6) (WMD = ���0.039 pg/ml, 95% CI: ���0.233 to 0.156, P = 0.696), and tumor necrosis factor-�� (TNF-��) (WMD = 0.405 ng/ml, 95% CI: ���1.036 to 0.226, P = 0.209) after adding exercise to a weight-loss diet compared with a weight-loss diet alone. Subgroup analysis revealed that exercise plus a weight-loss diet significantly reduced TNF-�� in studies greater than 16 weeks in duration (WMD = ���0.742 ng/ml, 95% CI: ���1.384 to ���0.1, P = 0.024). This systematic review and meta-analysis indicate that exercise in addition to a weight-loss diet does not have a significant effect on further reducing inflammatory markers compared to a weight loss diet alone.

Objective There is no consensus of opinion if exercise beneficially affects sex hormones if added to weight-loss diets. The purpose of this study was to perform a systematic review and meta-analysis of controlled clinical trials to evaluate the effect of adding exercise to a hypo-caloric diet during a weight-loss program, on serum testosterone, estradiol, and sex hormone-binding globulin (SHBG) in adults with overweight/obesity. Design Systematic review and meta-analysis of the literature. Methods Online databases including PubMed/MEDLINE, EMBASE, Scopus, ISI Web of Science, and Google Scholar were searched up to April 2021. A random-effects model was applied to compare mean changes in sex hormones and SHBG between participants undergoing a hypo-caloric diet with or without exercise. Results In total, 9 eligible clinical trials with 462 participants were included. Out of these, seven, three, and four studies illustrated changes in testosterone, estradiol, and SHBG, respectively. The meta-analysis revealed that exercise had no significant effect on circulating testosterone (WMD = −0.03 nmol/L, 95% CI: −0.11, 0.06, P = 0.51), estradiol (WMD = −0.46 pg/mL, 95% CI: −1.57, 0.65, P = 0.42), and SHBG (WMD = 0.54 nmol/L, 95% CI: −2.63, 3.71, P = 0.74) when added to low-calorie diets. Conclusion The addition of exercise to a hypo-caloric diet provided no additional improvement in sex hormone profiles. Further, well-designed randomized controlled trials with longer follow-up periods in both sexes are recommended to confirm and expand the current results.

Novel coronavirus disease 2019 (COVID-19) has posed a crucial hazard to global health. The new species share similarities with the two previously emerged entities: severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) that have caused outbreaks in 2002 and 2012, respectively. Interestingly, all of these coronaviruses can cause potentially fatal respiratory syndromes, though behave differently in patients with cancer compared to patients without cancer. Accordingly, the present chapter aims to, through a systematic investigation, estimate the prevalence of cancer among COVID-19, SARS, and MERS confirmed cases. Our analysis based on data from 78 studies with SARS, MERS, and COVID-19 confirmed cases showed that the prevalence of cancer (4.94%) stands at fourth place after hypertension (20.8%), diabetes (11.39%), and cardiovascular diseases (7.46%). According to the findings of the present study, comorbidities are significantly more common in patients with MERS compared to patients with COVID-19 and SARS, and this was the cancer case as well. Further studies need to address whether or not patients with coronaviruses and cancer are different from patients with coronaviruses without cancer in terms of clinical manifestations, laboratory findings, outcomes, and men to women ratio.

Novel coronavirus disease 2019 (COVID-19) has posed a crucial hazard to global health. The new species share similarities with the two previously emerged entities: severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) that have caused outbreaks in 2002 and 2012, respectively. Interestingly, all of these coronaviruses can cause potentially fatal respiratory syndromes, though behave differently in patients with cancer compared to patients without cancer. Accordingly, the present chapter aims to, through a systematic investigation, estimate the prevalence of cancer among COVID-19, SARS, and MERS confirmed cases. Our analysis based on data from 78 studies with SARS, MERS, and COVID-19 confirmed cases showed that the prevalence of cancer (4.94%) stands at fourth place after hypertension (20.8%), diabetes (11.39%), and cardiovascular diseases (7.46%). According to the findings of the present study, comorbidities are significantly more common in patients with MERS compared to patients with COVID-19 and SARS, and this was the cancer case as well. Further studies need to address whether or not patients with coronaviruses and cancer are different from patients with coronaviruses without cancer in terms of clinical manifestations, laboratory findings, outcomes, and men to women ratio.

Background Exercise and weight loss diets are two independent non-pharmaceutical strategies used to improve several aspects of body composition and health. We plan to systematically review controlled clinical trials investigating weight loss diets alone compared to weight loss diets in conjunction with exercise on energy intake, body weight, body composition, cardiometabolic risk factors, sex hormones, and mental health. Methods and analysis PubMed/MEDLINE, EMBASE, ISI (Web of Science), Scopus, and Google Scholar will be searched to retrieve potential controlled clinical trials investigating the effects of exercise in conjunction with weight loss diets compared with weight loss diets alone on energy intake, body weight and composition (fat mass, fat-free mass), anthropometrics (waist circumference), cardiometabolic markers, sex hormones [testosterone, estradiol, and sex hormone binding globulin (SHBG)], liver and kidney enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), uric acid, blood urea nitrogen (BUN), glomerular filtration rate (GFR), quality of life, and depression in adults. The weighted mean difference (WMD) and its corresponding 95% confidence intervals (CIs) will be derived using random effects model. Several subgroup analyses based on follow-up duration, the health status of the participants, the diet used for weight loss, the exercise protocol, participants’ sex, and other possible variables will be conducted to explore possible sources of heterogeneity. Publication bias will be explored by inspecting funnel plots and by conducting asymmetry tests. Overall quality of the evidence will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Discussion We envisage that this systematic review and meta-analysis will provide valuable information regarding the effectiveness of adding exercise to weight loss diets. No primary data is going to be collected; therefore, ethical approval is not required. The resulting manuscripts will be disseminated in peer-reviewed journals and at international and national conferences. Systematic review registration The study protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO, Registration ID: CRD42020173434).

An efficient and simple synthesis of 2,4,5-trisubstituted imidazoles is achieved by three-component cyclocondensation of benzil, aldehyde, and ammonium acetate by using nanosilica-supported imidazolium ionic liquid as a catalyst under solvent-free conditions. The key advantages of this process are high to excellent yields, short reaction time, easy work-up, and the reusability of the catalyst.

A simple, efficient, and convenient one-step method for synthesis of Hantzsch 1,4-dihydropyridine, using Cu-doped ZnO nanocrystalline powder as a catalyst is reported. The method offers several advantages including excellent yields, green solvent, easy work-up, simplicity in operation and catalyst reusability.

Nanotechnology holds great potential in advanced water and wastewater treatment to improve treatment efficiency. Zinc oxide nanoparticles (ZnO NPs) have received considerable attention due to their unique antibacterial activities toward various microorganisms that are commonly found in the environment. In the present study, ZnO NPs were synthesized through both mechano-chemical and sol–gel methods. The synthesized ZnO NPs were characterized through X-ray diffraction and transmission electron microscopy techniques. Then, their antibacterial activities against separated wastewater bacteria were evaluated by determining the zone inhibitor, the minimum inhibitory concentration, and the minimum bactericidal concentration. The results were compared with those obtained from wastewater after chlorine disinfection and ultraviolet (UV) disinfection. These studies demonstrated that the antibacterial activity of ZnO NPs depends on the type and the strain of bacteria. They have also demonstrated that the activity increases as the concentration of ZnO NPs increases. Overall, the experimental results suggest that ZnO NPs can potentially be an antibacterial reagent to treat wastewater. They can particularly be applied as a complementary method with UV disinfection. Thus, they can be developed as antibacterial agents to improve wastewater quality.

Dyslipidemia is an important risk factor for cardiovascular disease (CVD) and an important cause of death in adults. Long-term follow-up studies have demonstrated that dietary fat consumption in children and adolescent is one of these risk factors of dyslipidemia in adulthood. The purpose of the current study was to assess the dietary fat intake of Iranian adolescents and their relationship with serum lipid profiles. In this population based cross-sectional study 717 adolescents (391 girls and 326 boys), aged 10 to 19 years, were randomly selected from the fourth phase of Tehran Lipid and Glucose Study (2008-2011). Usual dietary intakes were assessed using valid and reliable food frequency questionnaire and a fasting blood sample was given from all participants to analyze serum lipid profile. Among serum lipid levels, only triglyceride (TG) concentration was higher significantly in boys. In girls, the percent of energy intake from total fat, poly unsaturated fatty acid (PUFA), mono unsaturated fatty acid (MUFA) and trans fatty acids were higher significantly. After adjustment for sex and age, serum levels of TG and HDL-C showed a significant decreasing and increasing trend according to the quartiles of percent of energy intake from PUFA, respectively. No significant difference was observed between other fatty acids and serum lipid profile. In conclusion, although the percent of calorie intake from fat and different types of fatty acids have effect in determining serum lipids levels, but they are not the most important factors for determining the serum lipid profile.

One of the major epidemiologic public health problems is worldwide metabolic syndrome (MetS). Since the relationship between diet quality and MetS among adolescents in developing countries has not been well understood, the present study aimed to evaluate the association between diet quality, as measured by Healthy Eating Index (HEI-2005) and the prevalence of MetS and its risk factors in a group of Tehranian adolescents. This cross-sectional study was conducted on 706 adolescents, aged 10-19 years, within the framework of Tehran Lipid and Glucose Study in 2008-2011. Usual dietary intakes were assessed by valid and reliable semi-quantitative food frequency questionnaire and diet quality score was obtained based on HEI-2005. MetS was determined using the modified de Ferranti definition. There were 706 adolescents, aged 14.8±2.7 years. The overall prevalence of MetS in adolescents was 22.4%. Large waist circumference was the most common component of MetS in both girls and boys. After adjusting for age, sex, energy intake and physical activity, participants who were in the highest quartile of HEI-2005 compared with lowest quartile had lower prevalence of hypertriglyceridemia (OR: 0.62; CI 95%: 0.40-0.96 and P for trend= 0.02), and low serum HDL-C (OR: 0.62; CI 95%: 0.41-0.97 and P for trend= 0.02). No significant difference was observed in odds of MetS, large waist circumference, hyperglycemia and hypertension. Adolescents with dietary pattern more consistent with the HEI-2005, had lower prevalence of hypertriglyceridemia and low serum HDL-C.

Cu doped ZnO nanocrystalline powder (10 mol%) has been found to be an efficient catalyst for the one-pot multi-component synthesis of fully substituted new indeno[1,2-b]pyridines through a combination of 1,3-indandione, propiophenone or acetophenone derivatives, aromatic aldehydes, and ammonium acetate in ethanol/H2O at room temperature. The methodology is mild, efficient and high to excellent yielding.

Nowadays it is known that dietary imbalances are associated with non-communicable diseases which would be a major cause of worldwide deaths in 2020. This study was conducted to assess the dietary pattern of students who live in a dormitory in Kerman, Iran, based on Healthy Eating Index-2005 (HEI-2005).This cross-sectional study was conducted on 229 students who lived in the dormitory of Kerman University of Medical Science. The participants were recruited by multistage sampling. Their usual dietary intake was collected by using a valid food frequency questionnaire. The diet quality was calculated via HEI-2005. The HEI-2005 score was categorized into three groups: less than 50 (poor diet), between 50-70 (needs improvement) and more than 70 (good diet).The mean score of HEI-2005 in the present study was 64.22±8.98. 8.1% of the participants had poor diet, 63.4% had to improve their diet, and 28.5% enjoyed a good diet. The percent of energy intake from total fat, saturated fatty acid, solid fat and added sugar, and also sodium were significantly lower in the highest category of HEI-2005 than the lowest category. There was no significant difference in the intake of cholesterol, total vegetable and dairy products between the highest and lowest quartile categories.Majority of the participants need to improve their diet.Policy revisions and dietary interventions would require to promote diet quality and prevent non-communicable diseases in the future.

Obesity has become a public health problem in adolescents and could be a risk factor for both short-term and long-term health consequences. This study aimed to evaluate the relationship of Dietary Guidelines for Americans Adherence Index (DGAI), Healthy Eating Index-2005 (HEI-2005) and Healthy Eating Index-2010 (HEI-2010) with risk of obesity associated phenotypes in Tehranian adolescents. This cross-sectional study was conducted within the framework of the Tehran Lipid and Glucose Study, on 722 adolescents, aged 10-19 years. Usual dietary intakes were assessed by a food frequency questionnaire, and diet quality scores were obtained based on DGAI, HEI-2005 and HEI-2010. General obesity and cardio metabolic risk factors were defined according to the Centers of Disease Control and Prevention and de'Ferranti cut-offs, respectively. After adjusting for age, sex, energy intake and physical activity, compared to those in the lowest quartile, participants in the highest quartile of HEI-2010 had lower risk of general obesity (OR: 0.62; 95% CI: 0.38-0.93; Ptrend = 0.03) and central obesity (OR: 0.63; 95% CI: 0.44-0.95; Ptrend = 0.04). No association was observed between different types of obesity and scores of other diet quality indices. In conclusions, considering the role of HEI-2010 in decreasing the risk of obesity, these findings suggest that HEI-2010 may be useful for assessing diet-related progress in obesity prevention efforts.

A simple, efficient, and rapid method for high-yielding regioselective mono bromination of phenols and anilines has been achieved by treatment with N-bromasaccharin in the presence of a catalytic amount of tungstophosphoric acid.

A simple and convenient one-step method for synthesis of acridines and their derivatives from condensation of aromatic aldehydes, cyclic diketones, and aryl amines using Cu-doped ZnO nanocrystalline powder as a catalyst is reported. The present protocol provides several advantages such as good yields, short reaction time, easy workup, and simplicity in operation.

CD96, a cell surface antigen recently described to be preferentially expressed on acute myeloid leukemia (AML) leukemic stem cells (LSC) may represent an interesting target structure for the development of antibody-based therapeutic approaches. The v-regions from the CD96-specific hybridoma TH-111 were isolated and used to generate a CD96-specific single chain fragment of the variable regions (scFv). An affinity maturated variant resulting in 4-fold enhanced CD96-binding was generated by random mutagenesis and stringent selection using phage display. The affinity maturated scFv CD96-S32F was used to generate bivalent mini-antibodies by genetically fusing an IgG1 wild type Fc region or a variant with enhanced CD16a binding. Antibody dependent cell-mediated cytotoxicity (ADCC) experiments revealed that Fc engineering was essential to trigger significant effector cell-mediated lysis when the wild type scFv was used. The mini-antibody variant generated by fusing the affinity-maturated scFv with the optimized Fc variant demonstrated the highest ADCC activity (2.3-fold enhancement in efficacy). In conclusion, our data provide proof of concept that CD96 could serve as a target structure for effector cell-mediated lysis and demonstrate that both enhancing affinity for CD96 and for CD16a resulted in mini-antibodies with the highest cytolytic potential.

Phenols and anilines can be brominated regioselectively using N-bromosaccharin as brominating agent in the presence of tungstophosphoric acid as a catalyst.

Protein- or glyco-engineering of antibody molecules can be used to enhance Fc-mediated effector functions. ScFv-Fc fusion proteins (scFv-Fc) represent interesting antibody derivatives due to their relatively simple design and increased tissue penetration. Here, the impact of protein- and glyco-engineering on ADCC potency of a panel of human IgG1-based scFv-Fc was tested. Three matched sets of scFv-Fc variants targeting CD7, CD20 or HLA class II and optimized for CD16a binding by mutagenesis, lack of core-fucose, or their combination, were generated and functionally tested in comparison to the corresponding wild type scFv-Fc. Antigen binding activity was not compromised by altered glycosylation or Fc mutagenesis, whereas Fc binding to CD16a was significantly enhanced in the order: non-core fucosylated/Fc-mutated double-engineered≫Fc-mutated≥non-core-fucosylated>wild-type IgG1-Fc. All engineered variants triggered potent ADCC with up to 100-fold reduced EC50 values compared to non-engineered variants. Interestingly, double-engineered variants were similarly effective in triggering ADCC compared to single-engineered variants irrespective of their 1 log greater CD16a binding affinity. Thus, these data demonstrate that protein- and glyco-engineering enhances NK-cell mediated ADCC of scFv-Fc similarly and show that enhancing CD16a affinity beyond a certain threshold does not result in a further increase of NK-cell mediated ADCC.

Abstract 2843 Natural killer group 2 member D (NKG2D) is an important activating receptor controlling cytotoxicity of natural killer (NK) cells and T cells and plays an important role in immune surveillance against tumors. For redirecting NK cells to B-lymphoid tumor cells two recombinant bifunctional antibody-based fusion proteins were designed in order to coat malignant cells with ligands for NKG2D and attract NK cells. Therefore, a human CD20-directed single-chain fragment variable (scFv) was fused to NKG2D-specific ligands, either MHC class I chain-related protein A (MICA) or unique long 16-binding protein 2 (ULBP2). These two fully human fusion proteins, designated MICA:CD20 and ULBP2:CD20, respectively, were expressed in eukaryotic cells and purified to homogeneity. Size exclusion chromatography revealed that both purified proteins predominantly formed monomers. MICA:CD20 and ULBP2:CD20 specifically and simultaneously bound to CD20 and NKG2D and efficiently mediated lysis of lymphoma cell lines with mononuclear cells from healthy donors as effector cells. Analysis of the activation status of NKG2D-positive T cells and NK cells revealed that MICA:CD20 and ULBP2:CD20 activated resting NK cells, but not T cells, indicating that NK cells were the relevant effector cell population for the two molecules. In cytotoxicity assays using human NK cells from healthy donors, both agents sensitized lymphoma cell lines as well as fresh tumor cells for NK cell-mediated lysis. MICA:CD20 and ULBP2:CD20 induced lysis at low nanomolar concentrations with half maximum effective concentrations between 1 and 4 nM depending on target cells. Interestingly, ULBP2:CD20 exhibited a higher cytolytic potential than MICA:CD20 in terms of maximum lysis. Importantly, MICA:CD20 and ULBP2:CD20 induced lysis of 13/13 tested primary tumor cell samples from patients with different B cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma and marginal zone lymphoma. Interestingly, cell surface expression of endogenous MICA and ULBP2 was low or not detectable on fresh tumor cells. In addition, ULBP2:CD20 was also capable of inducing lysis of tumor cells in cytotoxicity experiments using autologous patient-derived NK cells as effector cells, indicating that the triggering signal was sufficient to overcome inhibition by interactions between killer cell immunoglobulin-like receptors and MHC class I molecules. Moreover, both MICA:CD20 and ULBP2:CD20 synergistically enhanced antibody-dependent cellular cytotoxicity (ADCC) by the monoclonal antibody daratumumab directed against CD38 which is co-expressed together with CD20 on certain B cell lymphomas. This approach of simultaneously triggering ADCC and natural cytotoxicity by these bifunctional fusion proteins may represent a promising strategy to achieve stronger NK cell-mediated antitumor responses. Disclosures: de Weers: Genmab : Employment. van De Winkel:Genmab: Employment. Parren:Genmab: Employment.