The conduct of blood donation drives became difficult amid novel coronavirus disease pandemic and national lockdown. Despite no restriction for the outdoor blood donation drives, voluntary blood donor organizations (VBDOs) and individual donors became apprehensive regarding the possible risk of spread of the infection during blood donation. Various confidence-building measures were taken to decrease this hesitation. Numerous preventive measures were taken at the blood bank and at the donation venue to limit the possible risk of the spread of infection. With the help of these measures, the confidence of the individual blood donors and the VBDOs was restored and multiple blood drives were organized.
Recent studies have described the remarkable clinical outcome of anti-CD19 chimeric antigen receptor (CAR) T cells in treating B-cell malignancies. However, over 50% of patients develop lifethreatening toxicities associated with cytokine release syndrome which may limit its utilization in low-resource settings. To mitigate the toxicity, we designed a novel humanized anti-CD19 CAR T cells by humanizing the framework region of single-chain variable fragment (scFv) derived from a murine FMC63 mAb and combining it with CD8a transmembrane domain, 4-1BB costimulatory domain, and CD3z signaling domain (h1CAR19-8BBz). Docking studies followed by molecular dynamics simulation revealed that the humanized anti-CD19 scFv (h1CAR19) establishes higher binding affinity and has a flexible molecular structure with CD19 antigen compared with murine scFv (mCAR19). Ex vivo studies with CAR T cells generated from healthy donors and patients with relapsed/ refractory B-cell acute lymphoblastic leukemia (B-ALL) expressing either h1CAR19 or mCAR19 showed comparable antitumor activity and proliferation. More importantly, h1CAR19-8BBz T cells produced lower levels of cytokines (IFNg, TNFa) upon antigen encounter and reduced the induction of IL6 cytokine from monocytes than mCAR19-8BBz T cells. There was a comparable proliferation of h1CAR19-8BBz T cells and mCAR19-8BBz T cells upon repeated antigen encounter. Finally, h1CAR19-8BBz T cells efficiently eliminated NALM6 tumor cells in a preclinical model. In conclusion, the distinct structural modification in CAR design confers the novel humanized anti-CD19 CAR with a favorable balance of efficacy to toxicity providing a rationale to test this construct in a phase I trial.
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