Durgin Joseph S, Henderson Fraser, Nasrallah MacLean P, Mohan Suyash, Wang Sumei, Lacey Simon F, Melenhorst Jan Joseph, Desai Arati S, Lee John Y K, Maus Marcela V, June Carl H, Brem Steven, O'Connor Roddy S, Binder Zev, O'Rourke Donald M
Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States.
Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States.
Front Oncol. 2021 May 7;11:669071. doi: 10.3389/fonc.2021.669071. eCollection 2021.
Autologous chimeric antigen receptor (CAR) T cells targeted to epidermal growth factor receptor variant III (CAR T-EGFRvIII) have been developed and administered experimentally to treat patients with IDH1 wildtype recurrent glioblastoma (rGBM) (NCT02209376). We report the case of a 59-year-old patient who received a single peripheral infusion of CAR T-EGFRvIII cells and survived 36 months after disease recurrence, exceeding expected survival for recurrent glioblastoma. Post-infusion histopathologic analysis of tissue obtained during a second stage surgical resection revealed immunosuppressive adaptive changes in the tumor tissue as well as reduced EGFRvIII expression. Serial brain imaging demonstrated a significant reduction in relative cerebral blood volume (rCBV), a measure strongly associated with tumor proliferative activity, at early time points following CAR T treatment. Notably, CAR T-EGFRvIII cells persisted in her peripheral circulation during 29 months of follow-up, the longest period of CAR T persistence reported in GBM trials to date. These findings in a long-term survivor show that peripherally administered CAR T-EGFRvIII cells can persist for years in the circulation and suggest that this cell therapy approach could be optimized to achieve broader efficacy in recurrent GBM patients.
靶向表皮生长因子受体变异体III的自体嵌合抗原受体（CAR）T细胞（CAR T-EGFRvIII）已被研发出来，并已通过实验性给药用于治疗异柠檬酸脱氢酶1（IDH1）野生型复发性胶质母细胞瘤（rGBM）患者（NCT02209376）。我们报告了一例59岁的患者，该患者接受了一次外周血输注CAR T-EGFRvIII细胞，在疾病复发后存活了36个月，超过了复发性胶质母细胞瘤的预期生存期。在第二阶段手术切除过程中获取的组织进行输注后组织病理学分析显示，肿瘤组织出现免疫抑制适应性变化以及表皮生长因子受体变异体III（EGFRvIII）表达降低。系列脑部成像显示，在CAR T治疗后的早期时间点，相对脑血容量（rCBV）显著降低，rCBV是一种与肿瘤增殖活性密切相关的指标。值得注意的是，在29个月的随访期间，CAR T-EGFRvIII细胞持续存在于她的外周循环中，这是GBM试验中迄今报告的CAR T细胞持续时间最长的。这位长期存活者的这些发现表明，外周给予的CAR T-EGFRvIII细胞可以在循环中持续数年，并提示这种细胞治疗方法可以优化，以在复发性GBM患者中获得更广泛的疗效。
