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. 2022 Sep 12;13:997482. doi: 10.3389/fimmu.2022.997482

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Copyright © 2022 Feng, Xu, Cinquina, Wu, Zhang, Sun, Chen, Tian, Song, Pinz, Wada, Jiang, Hanes, Ma and Zhang

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Efficiency of CD4-IL15/IL15sushi CAR T cells in Patient 1 with Sézary syndrome. (A) Chest skin appearance with marked erythema and swelling before treatment with CD4-IL15/IL15sushi CAR T cells. (B) Chest skin appearance on Day 28 post-infusion. (C) Leg skin appearance before treatment with CD4-IL15/IL15sushi CAR T cells. (D) Leg skin appearance on Day 28 post- infusion. (E) H&E staining of skin biopsy before treatment with CD4-IL15/IL15sushi CAR T cells, showing extensive lymphocytic infiltration. (F) H&E staining of skin biopsy 28 days after treatment, showing significantly diminished lymphocyte levels. (G) CD4 expression of leukemic Sézary cells in skin biopsy before treatment. (H) Diminished CD4 expression in skin biopsy 28 days after treatment. (I) CD3-CD4+ leukemic Sézary cells dramatically diminished within 20 days after infusion with CD4-IL15/IL15sushi CAR T cells. (J) Expansion of CD3+CD8+ cells within 8 days after infusion with CD4-IL15/IL15sushi CAR T cells. (K) Expansion of NK cells within 22 days after infusion. (L) Decreased Treg cells within 19 days after infusion. (M) Long-term expansion of CD3+CD8+ cells 1 year after infusion. (N) Decreased CD3-CD4+ cell counts in peripheral blood remained undetectable for the next year after treatment (orange curve), whereas CD3+CD4+ cells were depressed during the first month post-treatment followed by recovery in the next few months (blue curve) after treatment, which indicates that immune reconstitution can be observed post-treatment. (O) Transient expansion of NK cells to 84.41% during the first month post-treatment following by a gradual decrease until 6 months and maintenance of that level for 6 more months. (P) Initial suppression of B cells for 2 months followed by expansion.