Melanoma — Adjuvant autologous natural dendritic cell (nDC) vaccination

An oncolytic virus's inflammatory remodelling of the tumour microenvironment would recruit CAR T cells and improve their function in solid tumours.

Contrary to the hypothesis, VSV-mIFNβ infection caused attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite producing a robust proinflammatory shift in the chemokine profile.

Why it matched: same research area · mechanism: Adaptive immunity & tolerance · failed the same way: Held in the model species, not beyond it

The five-peptide cancer vaccine S-588410, given after curative resection of HLA-A*24:02-positive, node-positive esophageal squamous cell carcinoma, would prolong relapse-free survival.

Among 276 randomised patients, median relapse-free survival was 84.3 weeks with the vaccine vs 84.1 with placebo (P = 0.8156), and overall survival did not differ (P = 0.6533). The primary endpoint was not met.

Why it matched: similar wording · failed the same way: Held in the model species, not beyond it

ZBTB38, a transcription factor highly expressed in germinal centre B cells and plasma cells, would be needed for normal antibody responses, as related family members are.

Mice lacking ZBTB38 in blood cells had normal germinal centre B cell numbers, normal antibody responses after immunisation, and normal memory B cell recall. Very few genes changed in B cells without ZBTB38.

Why it matched: mechanism: Adaptive immunity & tolerance · failed the same way: Held in the model species, not beyond it

Depleting B cells with rituximab, on top of mycophenolate and corticosteroids, would raise the renal response rate in class III or IV lupus nephritis.

Overall renal response at week 52 was 56.9% with rituximab vs 45.8% with placebo (P=0.18), across 144 patients — the primary endpoint was not met.

Why it matched: similar wording · mechanism: Adaptive immunity & tolerance

Low-dose IL2 raises regulatory T cells, which reverse protein loss in the urine in animal models of nephrotic syndrome, so it would lower protein loss in children whose nephrotic syndrome resists all other drugs.

In 5 boys given six monthly cycles, IL2 raised regulatory T cells in some, but protein in the urine and kidney function did not change at any point. One child had an asthma attack after the first dose.

Why it matched: mechanism: Adaptive immunity & tolerance · failed the same way: Held in the model species, not beyond it