Extended Data Fig. 6. Multiply pretreated GCT patient with repeated response upon CLDN6 CAR-T cell + CARVac redosing.

The GCT patient (non-seminoma, yolk-sac subtype) had multiple lung metastases and rapidly progressing disease at accrual (increase in target sum of 40% between screening and ACT). Tumor biopsy and immunohistochemical analysis revealed 90% positivity for ≥2 + CLDN6 membrane staining. Following LD and ACT with 1 × 10⁷ CLDN6 CAR-T cells in combination with multiple doses of CARVac (green dashes lines in B and C) he showed the only PR observed in patients treated at this lower dose level. First suspected new lesions occurred at week 18 post-ACT (red circle). Upon confirmed progression 22 weeks post-ACT (DOR of 3.7 m) and as an on-treatment biopsy was 100% CLDN6 positive, the patient was redosed (28 weeks post first ACT) at DL1 + CARVac after LD. The patient experienced another PR for multiple weeks until new lesions were confirmed (red circle). a, CT scans showing response of lung lesions after the first (ACT1) and the redosing (ACT2). b, Local measurement of tumor marker AFP indicates an ideal response (50% reduction within 7 days) to treatment immediately starting after ACT, reaching normalization and persistence of control for ~18 weeks. c, CAR-T cell kinetics by quantitative PCR analysis of DNA extracted from peripheral blood mononuclear cells (PBMCs). Note transient elevations in CAR-T cell counts after CARVac administrations (dashed green lines). Total CAR-T cell counts were calculated based on white blood cell count on the days of blood drawing (if available) and an assumed blood volume of 5 L. b and c: vertical grey lines are (re)dosing with CAR-T cells, dashed green lines are dosing with CARVac. ACT, adoptive cell transfer; AFP, alpha-fetoprotein; GCT, germ cell tumor; PD, progressive disease; PR, partial response; WK, week.; ULN, upper limit of normal.