Department of Oncology, Wayne State University, Detroit, Michigan, USA.
Biol Blood Marrow Transplant. 2013 Jun;19(6):925-33. doi: 10.1016/j.bbmt.2013.03.010. Epub 2013 Mar 22.
A phase I trial of infusing anti-CD3 × anti-CD20 bispecific antibody (CD20Bi) armed activated T cells (aATC) was conducted in high-risk/refractory non-Hodgkin's lymphoma patients to determine whether aATC infusions are safe, affect immune recovery, and induce an antilymphoma effect. Ex vivo expanded ATC from 12 patients were armed with anti-CD20 bispecific antibody, cryopreserved, and infused after autologous stem cell transplantation (SCT). Patients underwent SCT after high-dose chemotherapy, and aATC infusions were started on day +4. The patients received 1 infusion of aATC per week for 4 weeks after SCT with doses of 5, 10, 15, and 20 × 10(9). aATC infusions were safe and did not impair engraftment. The major side effects were chills, fever, hypotension, and fatigue. The mean number of IFN-γ Enzyme-linked Immunosorbent Spots (ElSpots) directed at CD20 positive lymphoma cells (DAUDI, P = .0098) and natural killer cell targets (K562, P < .0051) and the mean specific cytotoxicity directed at DAUDI (P = .037) and K562 (P = .002) from pre-SCT to post-SCT were significantly higher. The increase in IFN-γ EliSpots from pre-SCT to post-SCT in patients who received armed ATC after SCT were significantly higher than those in patients who received SCT alone (P = .02). Serum IL-7, IL-15, Macrophage inflammatory protein (MIP)-1 beta, IP-10, MIP-1α, and Monokine induced by gamma interferone increased within hours after infusion. Polyclonal and specific antibodies were near normal 3 months after SCT. aATC infusions were safe and increased innate and specific antilymphoma cell immunity without impairing antibody recovery after SCT.
一项在高危/难治性非霍奇金淋巴瘤患者中输注抗 CD3 × 抗 CD20 双特异性抗体（CD20Bi）武装激活 T 细胞（aATC）的 I 期试验，旨在确定 aATC 输注是否安全、影响免疫恢复和诱导抗淋巴瘤效应。从 12 名患者中体外扩增的 ATC 被武装上抗 CD20 双特异性抗体，冷冻保存，并在自体干细胞移植（SCT）后输注。患者在接受大剂量化疗后进行 SCT，并在 SCT 后第 4 天开始每周输注 1 次 aATC，剂量为 5、10、15 和 20×10(9)。aATC 输注是安全的，不会损害植入。主要副作用是寒战、发热、低血压和疲劳。针对 CD20 阳性淋巴瘤细胞（DAUDI，P=0.0098）和自然杀伤细胞靶标（K562，P<0.0051）的 IFN-γ 酶联免疫斑点（ElSpots）的平均数量，以及针对 DAUDI（P=0.037）和 K562（P=0.002）的特异性细胞毒性的平均数量，从 SCT 前到 SCT 后均显著升高。SCT 后接受武装 ATC 治疗的患者与仅接受 SCT 的患者相比，从 SCT 前到 SCT 后 IFN-γ ElSpots 的增加量显著更高（P=0.02）。输注后数小时内，血清 IL-7、IL-15、巨噬细胞炎症蛋白（MIP）-1β、IP-10、MIP-1α 和 γ 干扰素诱导的单核细胞增多症增加。SCT 后 3 个月时，多克隆和特异性抗体接近正常。aATC 输注是安全的，可在不损害 SCT 后抗体恢复的情况下，增强先天和特异性抗淋巴瘤细胞免疫。
