Memory CD73(+)IgM(+)B cells protect againstPlasmodium yoelii infection and express Granzyme B
PLOS ONE
Authors: Parra, Marcela; Weitner, Megan; Yang, Amy; Akue, Adovi; Liu, Xia; Schmidt, Thomas; Allman, Windy R.; Akkoyunlu, Mustafa; Derrick, Steven C.
Abstract
To better understand anti-malaria protective immune responses, we examined the cellular mechanisms that govern protective immunity in a murinePlasmodium yoelii17X NL (PyNL) re-infection model. Initially, we confirmed that immune B cells generated during a primary PyNL infection were largely responsible for protection from a second PyNL infection. Using the previously identified memory B cell markers CD80, PD-L2, and CD73, we found an increase in the frequency of CD80(-)PD-L2(-)CD73(+)B cells up to 55 days after a primary PyNL infection and at 4-6 days following a second PyNL infection. Moreover, injection of enriched immune CD19(+)CD73(+)B cells into nonimmune mice were significantly more protective against a PyNL infection than CD73(-)B cells. Interestingly, a substantial fraction of these CD73(+)B cells also expressed IgM and granzyme B, a biomolecule that has been increasingly associated with protective responses against malaria.
Unstimulated apheresis for chimeric antigen receptor manufacturing in pediatric/adolescent acute lymphoblastic leukemia patients
JOURNAL OF CLINICAL APHERESIS
Authors: Jarisch, Andrea; Rettinger, Eva; Soerensen, Jan; Klingebiel, Thomas; Schaefer, Richard; Seifried, Erhard; Bader, Peter; Bonig, Halvard
Abstract
Autologous unstimulated leukapheresis product serves as starting material for a variety of innovative cell therapy products, including chimeric antigen receptor (CAR)-modified T-cells. Although it may be reasonable to assume feasibility and efficiency of apheresis for CAR-T cell manufacture, several idiosyncrasies of these patients warrant their separate analysis: target cells (mononuclear cells [MNC] and T-cells) are relatively few which may instruct the selection of apheresis technology, low body weight, and, hence, low total blood volume (TBV) can restrict process and product volume, and patients may be in compromised health. We here report outcome data from 46 consecutive leukaphereses in 33 unique pediatric patients performed for the purpose of CD19-CAR-T-cell manufacturing. Apheresis targets of 2x10(9)MNC/1x10(9)T-cells were defined by marketing authorization holder specification. Patient weight was 8 to 84 kg; TBV was 0.6 to 5.1 L. Spectra Optia apheresis technology was used. For 23 patients, a single apheresis sufficed to generate enough cells and manufacture CAR-T-cells, the remainder required two aphereses to meet target dose and/or two apheresis series because of production failure. Aphereses were technically feasible and clinically tolerable without serious adverse effects. The median collection efficiencies for MNC and T-cells were 53% and 56%, respectively. In summary, CAR apheresis in pediatric patients, including the very young, is feasible, safe and efficient, but the specified cell dose targets can be challenging in smaller children. Continuous monitoring of apheresis outcomes is advocated in order to maintain quality.