Corrigendum to "Rational engineering of an improved adenosine deaminase 2 enzyme for weaponizing T-cell therapies": [Immuno-Oncology and Technology 10 (2023) 100394].

[This corrects the article DOI: 10.1016/j.iotech.2023.100394.].

Rational engineering of an improved adenosine deaminase 2 enzyme for weaponizing T-cell therapies.

Adenosine is a potent immunosuppressive metabolite that accumulates in the extracellular space within solid tumors and inhibits the antitumor function of native immune cell responses as well as chimeric antigen receptor (CAR) T-cell therapies. Here, we show that engineered human cells can degrade extracellular adenosine through secretion of adenosine deaminase (ADA) enzymes-a possible therapeutic enhancement for CAR T cells. We first determine that the high-activity ADA1 isoform is naturally intracellularly restricted and show that the addition of canonical or computationally predicted secretory peptides did not allow for improved secretion. We did, however, determine that the lower-activity ADA2 isoform is naturally secreted. Thus, we utilized phylogenetic-based structural comparisons to guide a mutational survey of ADA2 active site residues, which when coupled with a high-throughput screen for enhanced ADA2-mediated extracellular adenosine rate allowed isolation of the most catalytically efficient ADA2 variant reported to date. When expressed by human cells, this variant exhibits 30× higher extracellular adenosine degradation activity than the wild-type enzyme. Finally, we demonstrate that Jurkat and CAR T cells engineered to express this secreted, high-activity ADA2 variant can degrade significant amounts of extracellular adenosine in vitro.

Crescentic glomerulonephritis in juvenile chronic arthritis.

Juvenile chronic arthritis (JCA) was diagnosed in 2 young girls. In one of them, antinuclear antibodies (ANA) were strongly positive during the course of erosive polyarthritis. After 5 years followup, severe renal insufficiency occurred. Antineutrophil cytoplasmic antibodies (ANCA) were positive with a perinuclear pattern on indirect immunofluorescence (IIF) and antimyeloperoxidase (MPO) specificity. Renal biopsy showed severe crescentic glomerulonephritis without significant deposits on IIF. Treatment consisted of prednisone and monthly intravenous cyclophosphamide pulse. Renal failure worsened and hemodialysis was necessary. A 2nd patient was referred for polyarthritis with positive rheumatoid factors without positive ANA. The presence of microscopic hematuria led to the discovery of crescentic glomerulonephritis with positive ANCA of anti-MPO specificity. At latest examination, after prednisone for 10 months and azathioprine for 6 months, the patient had moderate proteinuria with normal renal function. These observations emphasize that in juvenile onset chronic polyarthritis, renal microscopic angiitis with ANCA of anti-MPO specificity may occur.

[Extracapillary glomerulonephritis secondary to D-penicillamine. Apropos of 1 case and review of the literature]. / Glomérulonéphrites extracapillaires secondaires à la D-pénicillamine. A propos d'une observation et revue de la littérature.

Extracapillary glomerulonephritis was diagnosed in a 51-year-old woman after 11 months of D-Penicillamine treatment given for systemic sclerosis. Antineutrophil cytoplasmic antibodies specific for myeloperoxydase were detected. Penicillamine was stopped and the patient was treated with plasma exchanges, cyclophosphamide and corticosteroids. The renal function progressively deteriorated leading to end stage requiring dialysis. Previous reports of extracapillary glomerulonephritis after D-penicillamine are analysed. Several cases with alveolar haemorrhage are consistent with the diagnosis of microscopic polyangiitis.