The cancer-testis antigen NY-ESO-1 is a potential target antigen for immune therapy expressed in a subset of patients with multiple myeloma. We generated chimeric antigen receptors (CARs) recognizing the immunodominant NY-ESO-1 peptide 157-165 in the context of HLA-A*02:01 to re-direct autologous CD8(+) T cells towards NY-ESO-1(+) myeloma cells. These re-directed T cells specifically lysed NY-ESO-1(157-165)/HLA-A*02:01-positive cells and secreted IFNγ. A total of 40% of CCR7(-) re-directed T cells had an effector memory phenotype and 5% a central memory phenotype. Based on CCR7 cell sorting, effector and memory CAR-positive T cells were separated and CCR7(+) memory cells demonstrated after antigen-specific re-stimulation downregulation of CCR7 as sign of differentiation towards effector cells accompanied by an increased secretion of memory signature cytokines such as IL-2. To evaluate NY-ESO-1 as potential target antigen, we screened 78 bone marrow biopsies of multiple myeloma patients where NY-ESO-1 protein was found to be expressed by immunohistochemistry in 9.7% of samples. Adoptively transferred NY-ESO-1-specific re-directed T cells protected mice against challenge with endogenously NY-ESO-1-positive myeloma cells in a xenograft model. In conclusion, re-directed effector- and central memory T cells specifically recognized NY-ESO-1(157-165)/ HLA-A*02:01-positive cells resulting in antigen-specific functionality in vitro and in vivo.

Background Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47–90% of the patients and lung cancer in 46.8% of the patients. Objective Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE. Methods We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data. Results Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers. Conclusion CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients.

Introduction: Since pregnancy in women with pulmonary arterial hypertension (PAH) is associated with a high risk of morbidity and mortality, it is recommended that pregnancy should be avoided in PAH. However, some women with mild PAH may consider this recommendation as unsuitable. Unfortunately knowledge on pregnancy outcomes and best management of PAH during pregnancy is limited.Methods: Data from all women with PAH who were followed during pregnancy by a multidisciplinary team at a tertiary referral center for PAH and who delivered between 2004 and 2020 were retrospectively analyzed in a case series. PAH risk factor profiles including WHO functional class (WHO-FC), NT-pro-BNP, echocardiographic pulmonary arterial pressure (PAP) and right heart function were analyzed prior to, during and following pregnancy.Results: In seven pregnancies of five women with PAH (median age 29 (27; 31) years), there were no abortions or terminations. Five pregnancies were planned (all in WHO-FC I-II), two incidental (WHO-FC II, III). During pregnancy none of the women had complications or clinical worsening of PAH. After a median pregnancy duration of 37 1/7 weeks all gave birth to healthy babies by cesarean section in spinal anesthesia. During pregnancy, PAP tended to increase, whilst the course of WHO-FC and NT-pro-BNP were variable and no trend could be detected.Conclusion: Women with PAH with a low risk profile closely followed by a multidisciplinary team had a favorable course during and after pregnancy, resulting in successful deliveries of healthy newborns.

Background: Patients with unrepaired cyanotic congenital heart disease (CHD) suffer from aggravated hypoxemia during exercise. We tested the hypothesis that supplemental oxygen improves exercise performance in these patients. Methods: In this randomized, sham-controlled, single-blind, cross-over trial cyanotic CHD-patients underwent four cycle exercise tests to exhaustion, while breathing either oxygen-enriched (FiO 2 0.50, oxygen) or ambient air (FiO 2 0.21, air) using incremental (IET) or constant work-rate (CWRET) exercise test protocols (75% of maximal work rate achieved under FiO 2 0.21). Pulmonary gas-exchange, electrocardiogram, arterial blood gases, oxygen saturation (SpO 2 ), cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. Results: We included seven patients with cyanotic CHD (4 Eisenmenger syndrome, 3 unrepaired cyanotic defects, 4 women) median (quartiles) age 36 (32;50) years, BMI 23 (20;26) kg/m 2 and SpO 2 at rest 87 (83;89) %. When comparing supplemental oxygen with air during exercise, maximal work-rate in IET increased from 76 (58;114) Watts to 83 (67;136) Watts, median difference 9 (0;22) W (p = 0.046) and CWRET-time increased from 412 s (325;490) to 468 s (415;553), median increase 56 (39;126) s (p = 0.018). In both IET and CWRET SpO 2 was significantly higher and ventilatory equivalent for carbon dioxide significantly lower at end-exercise with oxygen compared to air, whereas CTO and QMTO did not significantly differ. Conclusions: Patients with cyanotic CHD significantly improved their exercise performance, in terms of maximal work-rate and endurance time along with an improved arterial oxygenation and ventilatory efficiency with supplemental oxygen compared to air.

There is an urgent need to develop drugs and vaccines to counteract the effects of the new coronavirus SARS-CoV-2 and adequately treat the corona virus disease (COVID-19). As these drugs are still under investigation, research also focuses on existing medication with proven effectiveness in other coronaviral diseases. The advantages of existing therapeutic drugs that are currently approved (for other indications) are the known safety profile, general availability and relatively lower costs involved in extending the purpose to a new disease. Calcineurin inhibitors (CNI) are drugs that have shown effectiveness in several coronaviral diseases, and are well-known and widely used drugs in transplant medicine. The aim of this narrative review is to present the current evidence of CNI in coronaviral diseases, the biophysiology of CNI and to suggest possible ways to study CNI as a new treatment option for COVID-19. We searched original papers, observational studies, case reports, and meta-analyses published between 2000 and 2020 in English in the PubMed database and Google Scholar using the keywords: (coronavirus), (treatment), (MERS), (SARS), (COVID-19), (tacrolimus), (ciclosporin), (cyclosporin) AND (calcineurin inhibitor). We excluded studies in patients with clear indications for immunosuppressive therapy. Additionally, we searched in the preprint servers and the World Health Organization bulletin. Ten studies were identified and included. Calcineurin inhibitor therapy has been suggested to be effective for coronaviral diseases in different settings. The results are summarized in a table. CNI should be investigated as a first treatment option based on evidence of direct antiviral effects and its properties preventing severe systemic hyperinflammation, as has been observed in COVID-19 with predominantly pulmonary immunopathological changes.