27 June 2023 in Cancer Immunology Research
Vγ9Vδ2 T cells are effector cells with proven antitumor efficacy against a broad range of cancers. This study aimed to assess the antitumor activity and safety of a bispecific antibody directing Vγ9Vδ2 T cells to EGFR-expressing tumors. An EGFR-Vδ2 bispecific T-cell engager (bsTCE) was generated, and its capacity to activate Vγ9Vδ2 T cells and trigger antitumor activity was tested in multiple in vitro, in vivo, and ex vivo models. Studies to explore safety were conducted using cross-reactive surrogate engagers in nonhuman primates (NHP). We found that Vγ9Vδ2 T cells from peripheral blood and tumor specimens of patients with EGFR+ cancers had a distinct immune checkpoint expression profile characterized by low levels of PD-1, LAG-3, and TIM-3. Vγ9Vδ2 T cells could be activated by EGFR-Vδ2 bsTCEs to mediate lysis of various EGFR+ patient–derived tumor samples, and substantial tumor growth inhibition and improved survival were observed in in vivo xenograft mouse models using peripheral blood mononuclear cells (PBMC) as effector cells. EGFR-Vδ2 bsTCEs exerted preferential activity toward EGFR+ tumor cells and induced downstream activation of CD4+ and CD8+ T cells and natural killer (NK) cells without concomitant activation of suppressive regulatory T cells observed with EGFR-CD3 bsTCEs. Administration of fully cross-reactive and half-life extended surrogate engagers to NHPs did not trigger signals in the safety parameters that were assessed. Considering the effector and immune-activating properties of Vγ9Vδ2 T cells, the preclinical efficacy data and acceptable safety profile reported here provide a solid basis for testing EGFR-Vδ2 bsTCEs in patients with EGFR+ malignancies.
23 November 2010 in Vox Sanguinis
Background and Objectives The use of umbilical cord blood (UCB) for transfusion purposes has gained interest the past years. UCB transfusion could serve premature infants, who often need transfusions early in life.Material and Methods We investigated the suitability of different storage media. UCB was collected after 25 0/7–35 6/7 gestational weeks and centrifuged to concentrate red cells subsequently stored in saline–adenine–glucose–mannitol (SAGM), or in additive solution‐3 (AS‐3), or stored as whole blood in citrate–phosphate–dextrose–adenine‐1. Quality parameters were measured at 7 day intervals during 35 days and compared to the standard RBC product.Results White‐blood‐cell‐ and platelet counts were higher in the UCB products. In the fractionated units, haemolysis remained below 1·0% in 64% after 14 days, and in 30% after 21 days. Storage in SAGM or AS‐3 showed similar quality. Whole blood UCB showed better pH and haemolysis rates after 21 days.Conclusion UCB can be processed into autologous products for premature infants. Shelf‐life is limited to 14–21 days and compares unfavourably to stored whole blood. Considering the early transfusion needs in these infants, a short shelf‐life would not be a practical objection.