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Patients with sickle cell anemia (SCA) have long been discouraged from physical activity (PA). The aim of the present study was to assess the impact of increasing daily step counts on physical fitness, pain and vascular function in patients with SCA. Thirty-eight patients with SCA were recruited and equipped with a Fitbit wrist-worn accelerometer-based PA tracker for 5 weeks to objectively quantify their baseline daily step counts. Patients were then randomly assigned to one of the three groups: 1) control group: no specific information regarding PA was given for 8 weeks (N=12); 2) PA1 group: daily step counts increased by 25% of baseline for 8 weeks (N=12); 3) PA2 group: daily step counts increased by 25% for 4 weeks, then by 50% for 4 additional weeks (N = 14). Pain intensity and frequency decreased after the intervention in the PA1 and PA2 groups. In addition, patients from these two groups increased the distance walked in 6 minutes. Arterial stiffness decreased in both PA1 and PA2 groups, without any change in the autonomic nervous system activity. Several inflammatory markers slightly decreased in the PA2 group. Incubation of cultured endothelial cells with patient plasma showed a decrease in the percentage of ICAM-1 positive cells in the PA2 group. This study is the first to show that increasing daily PA by a simple way (i.e., increasing daily step count of 25-50%) for 8 weeks is sufficient to decrease pain, and improve physical condition and vascular function of patients with SCA.
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We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a highrisk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T-cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to both an anti-IGLV3-21R110 Fab and an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors. R110-bsAb spared polyclonal human B cells (as opposed to CD19-targeting blinatumomab) as well as CD34+ human stem cells. Yet, R110-bsAb induced lower T-cell activation than blinatumomab with primary CLL cells likely due to lower expression of target antigen. In vivo, R110- bsAb specifically killed IGLV3-21R110-expressing cell lines and CLL cells while sparing peripheral blood mononuclear cells. These findings highlight bispecific antibodies as a potential off-the-shelf immunotherapy for high-risk CLL patients, offering selective targeting while preserving healthy B cells.
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