Human Cancer-Targeted Immunity via Transgenic Hematopoietic Stem Cell Progeny

Analysis of a patient biopsy from the clinical trial (NCT03240861), a first-in-human study of transgenic NY-ESO-1 TCR- T cells and NY-ESO-1 TCR+ sr39tk autologous hematopoietic stem cells tandem therapy for solid tumors after myeloablative conditioning chemotherapy with busulfan and fludarabine. Single-cell RNAseq and single-cell ATACseq analysis from peripheral blood mononuclear cells obtained from subject NYSCT-03.]]>
Subjects must be HLA-A*0201, have locally advanced (unresectable stage IIIc) or metastatic malignancies (stage IV), whose tumor express NY-ESO-1, and who have exhausted (or ineligible) all current available treatment options, age greater than or equal to 16, clinical performance status of ECOG 0 or 1, no active autoimmune diseases, and be seronegative for HIV, Hepatitis B and C (seropositive subjects would be more likely to have toxic effects from the conditioning chemotherapy). Patients should not have received any systemic treatment for cancer within 30 days of starting conditioning chemotherapy in this trial. Patients must have adequate bone marrow and major organ function to undergo a PBSC transplant.]]>

本研究针对临床试验（NCT03240861）中的患者活检样本开展分析，该试验为首次人体研究，评估转基因NY-ESO-1 TCR-T细胞与NY-ESO-1 TCR阳性sr39tk自体造血干细胞串联疗法，用于经白消安与氟达拉滨行清髓性预处理化疗后的实体瘤治疗。本分析针对受试者NYSCT-03的外周血单个核细胞（peripheral blood mononuclear cells）开展单细胞RNA测序（single-cell RNAseq）与单细胞ATAC测序（single-cell ATACseq）。
受试者需满足以下全部条件：人类白细胞抗原A*0201阳性；患有局部晚期（不可切除IIIC期）或转移性（IV期）恶性肿瘤，且肿瘤表达NY-ESO-1；已穷尽所有现有可用治疗方案（或不符合现有治疗方案的入选资格）；年龄≥16岁；东部肿瘤协作组（ECOG）体能状态评分为0或1分；无活动性自身免疫性疾病；HIV、乙型肝炎及丙型肝炎血清学检测均为阴性（血清学阳性受试者更易出现预处理化疗相关毒性反应）；在本试验开始预处理化疗前30天内，未接受过任何癌症系统性治疗；骨髓及主要器官功能满足外周血干细胞（peripheral blood stem cell, PBSC）移植要求。