Grain Audrey, Ollier Jocelyn, Guillaume Thierry, Chevallier Patrice, Le Calvez Baptiste, Eveillard Marion, Clémenceau Béatrice
Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, CRCI2NA, F-44007 Nantes, France.
Paediatric Haematology and Oncology Nantes University Hospital, 44093 Nantes, France.
Biomedicines. 2023 Jan 25;11(2):345. doi: 10.3390/biomedicines11020345.
Therapeutic options for CD19 relapses after anti-CD19 CAR-T cells are still debated; second infusion of anti-CD19 CAR-T cells, therapeutic antibodies, or targeted therapies can be discussed. Here, we explore the immunophenotyping and lysis sensitivity of CD19 ALL relapse after anti-CD19 CAR-T cells and propose different therapeutic options for such a high-risk disease.
Cells from successive B-ALL relapses from one patient were collected. A broad immunophenotype analysis was performed. Cr cytotoxic assays, and long-term killing assays were conducted using T-cell effectors that are capable of cytotoxicity through three recognition pathways: antibody-dependent cell-mediated cytotoxicity (ADCC), anti-CD19 CAR-T, and TCR.
Previously targeted antigen expression, even if maintained, decreased in relapses, and new targetable antigens appeared. Cytotoxic assays showed that ALL relapses remained sensitive to lysis mediated either by ADCC, CAR-T, or TCR, even if the lysis kinetics were different depending on the effector used. We also identified an immunosuppressive monocytic population in the last relapse sample that may have led to low persistence of CAR-T.
CD19 relapses of ALL remain sensitive to cell lysis mediated by T-cell effectors. In case of ALL relapses after immunotherapy, a large immunophenotype will make new therapies possible for controlling such high risk ALL.
抗CD19嵌合抗原受体T细胞（CAR-T）治疗后CD19复发的治疗选择仍存在争议；可以讨论再次输注抗CD19 CAR-T细胞、治疗性抗体或靶向治疗。在此，我们探讨抗CD19 CAR-T细胞治疗后CD19急性淋巴细胞白血病（ALL）复发的免疫表型分析和裂解敏感性，并针对这种高危疾病提出不同的治疗选择。
收集一名患者连续B-ALL复发的细胞。进行广泛的免疫表型分析。使用能够通过三种识别途径产生细胞毒性的T细胞效应器进行铬释放细胞毒性试验和长期杀伤试验：抗体依赖性细胞介导的细胞毒性（ADCC）、抗CD19 CAR-T和T细胞受体（TCR）。
先前靶向的抗原表达在复发时即使得以维持也会降低，并且会出现新的可靶向抗原。细胞毒性试验表明，ALL复发对ADCC、CAR-T或TCR介导的裂解仍敏感，尽管裂解动力学因所用效应器而异。我们还在最后一次复发样本中鉴定出一个免疫抑制性单核细胞群体，其可能导致CAR-T的低持久性。
ALL的CD19复发对T细胞效应器介导的细胞裂解仍敏感。在免疫治疗后ALL复发的情况下，全面的免疫表型分析将使控制这种高危ALL的新疗法成为可能。
