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Wentworth McClanahan posted an update a month ago
On-target off-tumor toxicity impedes the clinical application of chimeric antigen receptor-modified T cells (CAR-T cells) in the treatment of solid tumors. Previous reports proved that the combinatorial antigen recognition strategy could improve the safety profile of CAR-T cells by targeting two different tumor-associated antigens (TAAs), one as a CAR-T targeted antigen and the other as a chimeric costimulatory receptor (CCR) ligand. The programmed death-ligand 1 (PD-L1, also known as B7-H1) is preferentially overexpressed on multiple tumors, it will be highly interesting to explore the potential of PD-L1 as a universal target for designing CCR.
A novel dual-targeted CAR, which is composed of first-generation CD19/HER2 CAR with CD3ζ signaling domain and PD-L1 CCR containing the CD28 costimulatory domain, was constructed and delivered into T cells by pseudotyped lentivirus. The cytokine release, cytotoxicity and proliferation of dual-targeted CAR-T cells were tested in vitro, and their safety and therapeutof on-target off-tumor toxicity while retaining their potent antitumor efficacy in the treatment of PD-L1
solid tumors.
Our observations demonstrated that PD-L1 could be used as a universal target antigen for designing CCR, and the dual-targeted CAR-T cells equipped with PD-L1 CCR could be used to reduce the risk of on-target off-tumor toxicity while retaining their potent antitumor efficacy in the treatment of PD-L1+ solid tumors.
Few studies have explored the relationship between food habits and the risk of gestational diabetes mellitus (GDM) in women from India. We aimed to investigate the associations of food habits and the risk of GDM.
As part of the MAASTHI prospective cohort study in urban Bengaluru, India, pregnant women between 18 and 45 years, less than 36 weeks of gestation were included. During baseline, the participant’s age, education, physical activity levels, and food habits were recorded. Screening of GDM was done by the World Health Organization diagnostic criteria using a 2-h 75-g oral glucose tolerance test between the 24th-36th weeks of gestation.
We included 1777 pregnant women in the study. We show that 17.6% of the women had GDM, of which 76.7% consume red meat. Red meat consumption was associated with an increased risk of GDM (aRR = 2.1, 95% CI 1.5, 2.9) after adjusting for age, family history of diabetes and socioeconomic status.
The high intake of red meat consumption in pregnancy needs further examination. Also, future evaluations should consider evaluating the risk of red meat consumption against the combined effect of inadequate consumption of vegetables, fruits, and dairy products in pregnant women. Interventions to educate women in lower socioeconomic status on inexpensive, seasonal, and healthy food might be helpful.
The high intake of red meat consumption in pregnancy needs further examination. Bleximenib in vivo Also, future evaluations should consider evaluating the risk of red meat consumption against the combined effect of inadequate consumption of vegetables, fruits, and dairy products in pregnant women. Interventions to educate women in lower socioeconomic status on inexpensive, seasonal, and healthy food might be helpful.
Micronutrient deficiencies affect many children in low-income settings due primarily to over-reliance on complementary foods low in nutrients. Home-fortification (HF) could improve children’s diet quality in these settings. The Ghana Health Service, supported by UNICEF, integrated the pilot Micronutrient Powder Initiative (MPI) into Child Welfare Clinic (CWC) services in four districts (Tain, Tolon, Talensi, and Ho West), whereby micronutrient powder (MNP) is supplied for HF for children aged 6-23 months attending CWCs. This study’s main aim was to identify the facilitators, barriers and “lessons learned” after 2 years of program implementation.
This was a qualitative cross-sectional study. MNP distributed and children enrolled were obtained from program records. Primary data were collected from November to December 2019 and included, by district interviews with senior program staff; key informant interviews and focus group discussion with caregivers in each of 6 sub-districts; and discussions workshop wirontline workers; and perceived MNP side-effects. Key lessons learned are incorporating MNPs into CWC services is feasible, acceptable, and could reduce child micronutrient deficiencies in program districts; and MPI’s success requires stronger community sensitization, equipping frontline workers to advise caregivers and manage side-effects, and consciously identifying and managing logistical challenges.
Further research is needed to evaluate the effectiveness of the MPI in reducing micronutrient deficiencies among 6-23-months-olds in Ghana.
Further research is needed to evaluate the effectiveness of the MPI in reducing micronutrient deficiencies among 6-23-months-olds in Ghana.Although anti-CD19 chimeric antigen receptor (CAR) T-cell therapy shows good efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), it fails to improve long-term leukemia-free survival (LFS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR T-cell therapy has emerged as a promising strategy to prolong LFS. Nevertheless, which patients are likely to benefit from consolidative allo-HSCT, as well as the optimal therapeutic window, remain to be explored. Recent clinical data indicate that patients with complex karyotypes, adverse genes, and high pre-infusion minimal residual disease (MRD) by flow cytometry in the bone marrow, were at high risk of relapse after CAR T-cell therapy. High pre-lymphodepletion lactate dehydrogenase, low pre-lymphodepletion platelet count, absence of fludarabine in lymphodepletion, persistent leukemic sequence by high throughput sequencing in bone marrow after CAR T-cell infusion, and early loss of CAR T cells have also been linked to relapse after CAR T-cell therapy. In patients having these risk factors, consolidative allo-HSCT after CAR T-cell therapy may prolong LFS. Allo-HSCT provides optimal clinical benefit in patients with MRD-negative complete remission, typically within three months after CAR T-cell therapy. Herein, we summarize the clinical data on consolidative allo-HSCT after anti-CD19 CAR T-cell therapy, as well as the potential factors associated with allo-HSCT benefit. We also discuss the optimal therapeutic window and regimen of consolidative allo-HSCT. Finally, and most importantly, we provide recommendations for the assessment and management of r/r B-ALL patients undergoing anti-CD19 CAR T-cell therapy.