Morse Michael A, Nair Smita K, Mosca Paul J, Hobeika Amy C, Clay Timothy M, Deng Yuping, Boczkowski David, Proia Alan, Neidzwiecki Donna, Clavien Pierre-A, Hurwitz Herbert I, Schlom Jeffrey, Gilboa Eli, Lyerly H Kim
Department of Medicine, Medical Center, Box 3233, Durham, North Carolina 27710, USA.
Cancer Invest. 2003 Jun;21(3):341-9. doi: 10.1081/cnv-120018224.
Immunizations with dendritic cells (DC) transfected with RNA encoding tumor antigens induce potent tumor antigen-specific immune responses in vitro and in murine models. We performed a phase I study of patients with advanced carcinoembryonic antigen (CEA)-expressing malignancies followed by a phase II study of patients with resected hepatic metastases of colon cancer to assess safety and feasibility of administering autologous DC loaded with CEA mRNA. The immunizations were well tolerated. Of the 24 evaluable patients in the dose-escalation phase, there was 1 complete response (by tumor marker), 2 minor responses, 3 with stable disease, and 18 with progressive disease. In the phase II study, 9 of 13 patients have relapsed at a median of 122 days. Evidence of an immunologic response was demonstrated in biopsies of DC injection sites and peripheral blood of selected patients. We conclude that it is feasible and safe to administer mRNA-loaded DC to patients with advanced malignancies.
用编码肿瘤抗原的RNA转染树突状细胞（DC）进行免疫接种，在体外和小鼠模型中可诱导强烈的肿瘤抗原特异性免疫反应。我们对晚期表达癌胚抗原（CEA）的恶性肿瘤患者进行了I期研究，随后对结肠癌肝转移切除患者进行了II期研究，以评估给予负载CEA mRNA的自体DC的安全性和可行性。免疫接种耐受性良好。在剂量递增阶段的24例可评估患者中，有1例完全缓解（根据肿瘤标志物），2例轻微缓解，3例病情稳定，18例病情进展。在II期研究中，13例患者中有9例在中位122天时复发。在选定患者的DC注射部位活检和外周血中证实了免疫反应的证据。我们得出结论，对晚期恶性肿瘤患者给予负载mRNA的DC是可行且安全的。
