We assessed both non- and peptide-specific immune responses in prostate cancer patients before and after immunotherapy with dendritic cells exogenously pulsed with the prostate-specific membrane ...antigen-derived peptides, PSM-P1 and PSM-P2. For all subjects, we observed that clinical responses were strongly associated with two indicators of immunocompetence: skin test responses to recall antigens and cytokine secretion by T cells after nonspecific stimulation. In a subset of responders, we observed cytokine secretion or cytotoxicity against the immunizing peptides or an immunodominant epitope from an influenza recall antigen. The clinical results support the use of monitoring for overall immunocompetence to help determine why a patient has or has not responded to therapy. Moreover, it could be useful as an inclusion criterion to select those more likely to benefit from treatment.
CD20-directed therapy with rituximab is effective in many patients with malignant lymphoma or follicular lymphoma. However, relapse frequently occurs within 1 year, and patients become increasingly ...refractory to retreatment. Our purpose was to produce a compact, single-chain CD20-targeting immunotherapeutic that could offer therapeutic advantages in the treatment of B-cell lymphoma.
Rituximab is a chimeric antibody containing two heavy chains and two light chains. Here, we describe the properties of TRU-015, a small modular immunopharmaceutical specific for CD20, encoded by a single-chain construct containing a single-chain Fv specific for CD20 linked to human IgG1 hinge, CH2, and CH3 domains but devoid of CH1 and CL domains.
TRU-015 mediates potent direct signaling and antibody-dependent cellular cytotoxicity but has reduced size and complement-mediated cytotoxicity activity compared with rituximab. TRU-015 is a compact dimer of 104 kDa that comigrates with albumin in size exclusion chromatography and retains a long half-life in vivo. TRU-015 induced growth arrest in multiple B lymphoma cell lines in vitro and showed effective antitumor activity against large, established subcutaneous Ramos or Daudi xenograft tumors in nude mice. TRU-015 also showed rapid, dose-dependent, and durable depletion of peripheral blood B cells following single-dose administration to nonhuman primates.
These results indicate that TRU-015 may improve CD20-directed therapy by effectively depleting embedded malignant B cells and nonmalignant pathogenic B cells and do so with reduced complement activation.
Introduction: Emotional expressivity plays an important role in terms of communication and interpersonal relationships in the context of society. Our research aims at assessing the perception of ...emotional expressivity and its association with lifestyle changes during COVID-19 lockdown among university students in Lebanon.
Methodology: A total of 742 participants completed an anonymous online questionnaire including socio-demographic characteristics, lifestyle habits, and emotional expression evaluated through the Berkeley Expressivity Questionnaire (BEQ). Participants also reported their perception of the relationship between emotional expressivity and lifestyle changes experienced during lockdown.
Results: The expression of positive emotions was decreased among students who have a weight loss from decreased eating during lockdown. Moreover, significantly lower negative emotions and increased positive emotions were found to be associated respectively with the increase in quality and quantity of distance learning, which emphasizes the psychological investment in education. In terms of extensive time spent on TV and social media, results point towards increased emotional expressivity, particularly positive emotions and impulse facets. Finally, changes in social interaction during this period impacted all facets of emotional expressivity.
Conclusions: In the context of lockdown due to the pandemic, emotional aspects were associated by university students with lifestyle changes. Our research highlights the beneficial role of social networking, distance learning, physical activity, and well-balanced nutrition on emotional regulation in this particularly stressful situation, thus the importance of a global approach to emotional expressivity including the social aspects and biological ones.
4-1BB (CD137) is an activation-induced costimulatory receptor that regulates immune responses of activated CD8 T and natural killer cells, by enhancing proliferation, survival, cytolytic activity, ...and IFNγ production. The ability to induce potent antitumor activity by stimulating 4-1BB on tumor-specific cytotoxic T cells makes 4-1BB an attractive target for designing novel immuno-oncology therapeutics. To minimize systemic immune toxicities and enhance activity at the tumor site, we have developed a novel bispecific antibody that stimulates 4-1BB function when co-engaged with the tumor-associated antigen 5T4. ALG.APV-527 was built on the basis of the ADAPTIR bispecific platform with optimized binding domains to 4-1BB and 5T4 originating from the ALLIGATOR-GOLD human single-chain variable fragment library. The epitope of ALG.APV-527 was determined to be located at domain 1 and 2 on 4-1BB using X-ray crystallography. As shown in reporter and primary cell assays in vitro, ALG.APV-527 triggers dose-dependent 4-1BB activity mediated only by 5T4 crosslinking. In vivo, ALG.APV-527 demonstrates robust antitumor responses, by inhibiting growth of established tumors expressing human 5T4 followed by a long-lasting memory immune response. ALG.APV-527 has an antibody-like half-life in cynomolgus macaques and was well tolerated at 50.5 mg/kg. ALG.APV-527 is uniquely designed for 5T4-conditional 4-1BB-mediated antitumor activity with potential to minimize systemic immune activation and hepatotoxicity while providing efficacious tumor-specific responses in a range of 5T4-expressing tumor indications as shown by robust activity in preclinical in vitro and in vivo models. On the basis of the combined preclinical dataset, ALG.APV-527 has potential as a promising anticancer therapeutic for the treatment of 5T4-expressing tumors.
Background. In Western countries, only a small proportion of patients with hepatocellular carcinoma (HCC) can be treated with surgical resection. For other patients, locoregional management by ...transcatheter oily chemoembolization seems to be useful and warrants evaluation.
Methods. One hundred and twenty‐seven French patients with an inoperable HCC were treated by transcatheter oily chemoembolization. The efficiency of the treatment was assessed by a comparison of this group with a group of 127 untreated patients. Each patient of the treated group was matched closely with an untreated patient for all the main clinical, anatomic, and biologic features that characterize the spontaneous evolution of HCC.
Results. The overall probabilities of survival in the treated group were 64%, 38%, 27%, and 27% at 1, 2, 3, and 4 years, respectively; those for the untreated group were 18%, 6%, and 5% at 1, 2 and 3 years, respectively (P < 0.0001). The survival was significantly increased in patients with Okuda Stage I and II disease (P < 0.0001), but not in those with Stage III. Karnofsky and Child‐Pugh scores remained stable during the follow‐up period and dropped only shortly before patients died.
Conclusion. Transcatheter oily chemoembolization is an efficient treatment for unresectable HCC for the palliation of symptoms as well as for the prolongation of survival with a good quality of life.
Purpose
Alexithymia, defined as the inability of a person to identify, describe and express emotions, has been found to influence glycemic control in type 2 diabetes patients (D2). The ...characteristics and influencing factors of alexithymia and the association of this psychological construct with D2 has not yet been studied in Lebanon where 14.6% of adults are diagnosed with the disease. This study aims at evaluating the prevalence of alexithymia and its relationship with glycemic control among Lebanese adults with D2.
Methods
Alexithymia was assessed in 104 patients diagnosed with D2 and 100 healthy controls using the 20-item Toronto Alexithymia Scale (TAS-20). The impact of alexithymia on glycemic control was evaluated using HbA1c values, fasting blood glucose levels, number of severe hyperglycemic episodes and hospitalizations for hyperglycemia within the past months.
Results
Alexithymia prevalence was significantly higher in D2 patients compared to controls (35.5% vs 15%). Patients with alexithymia showed higher levels of HbA1c and glucose in comparison to those without alexithymia. Consistently, significant positive correlations were found between the TAS-20 total and subscale scores and both HbA1c and glucose levels. Alexithymic patients had three times more severe hyperglycemic episodes and five times more hospitalizations for hyperglycemia compared to those without alexithymia. According to multivariate regression analysis, lifestyle factors alone were not found predictive of alexithymia in D2 patients.
Conclusion
Given the impact of alexithymia on D2 regulation, screening of alexithymia in case of D2 and appropriate psychological follow-up are important for a better prognosis, management and treatment of the disease.
Hepatitis C is poorly documented in migrants. The published studies mainly concern the screening in this population and are limited to some countries in Europe and North America. This study aimed to ...evaluate the characteristics and care of chronic hepatitis C in this population compared to the nonmigrant population, in the era of direct-acting antivirals (DAAs).
We performed a retrospective analysis based on data presented at the multidisciplinary team meetings of our tertiary care center between 2015 and 2019.
We included 277 migrant- and 1390 nonmigrant patients mono-infected with hepatitis C virus (HCV) and treated with DAAs. The majority of the migrants were from Eastern European countries. In multivariable analysis, BMI classes associated with more obesity (OR = 1.84; 95% CI, 1.37-2.49; P < 0.001) and therapeutic patient education (OR = 3.91; 95% CI, 2.38-6.49; P < 0.001) were positively associated with migrant status, whereas age (OR = 0.92; 95% CI, 0.90-0.94; P < 0.001), female gender (OR = 0.46; 95% CI, 0.28-0.74; P = 0.002), modes of contamination with less drug use, transfusion history or nosocomial risk, as well more unknown mode (OR = 0.70; 95% CI, 0.50-0.96; P = 0.031), alcohol consumption (OR = 0.48; 95% CI, 0.29-0.73; P = 0.001), types of structures with less care in a general hospital or health network of general practitioners and more care in a university hospital or primary addictology center (OR = 0.78; 95% CI, 0.60-0.99; P = 0.046) and opioid substitution therapy (OR = 0.25; 95% CI, 0.08-0.68; P = 0.008) were negatively associated with migrant status. The substained virologic response 12 was close to 97% in both groups.
Despite multiple differences in characteristics and therapeutic care between the two populations, the chances of healing hepatitis C were the same among migrant- compared with nonmigrant patients.
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