Brill T H, Kübler H R, von Randenborgh H, Fend F, Pohla H, Breul J, Hartung R, Paul R, Schendel D J, Gansbacher B
Institute for Experimental Oncology, Technical University, Klinikum rechts der Isar, Munich, Germany.
J Gene Med. 2007 Jul;9(7):547-60. doi: 10.1002/jgm.1051.
The purpose of this vaccine study was to determine the safety and feasibility of vaccination with an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and to evaluate the efficacy of inducing tumor-specific immune responses in HLA-A2-matched patients with hormone refractory prostate cancer (HRPC).
In a dose-escalating phase I study, HLA-A2-matched HRPC patients received four vaccinations of irradiated allogeneic LNCaP cells retrovirally transduced to secrete IL-2 and IFN-gamma at study day 1, 15, 29 and 92 and subsequently every 91 days unless tumor progression was evident.
Three patients receiving the first dose level (7.5 million cells) showed no evidence of dose-limiting toxicity or vaccine-related adverse events including autoimmunity. One of three patients receiving the second dose level (15 million cells) developed a transient self-limiting grade 3 local injection site reaction (ulceration) after the eighth vaccination. Vaccine-induced immune responses against a broad array of prostate tumor associated antigens were detected in all six patients. Two of the three patients receiving the higher dose showed a decline in serum prostate-specific antigen (PSA) values of more than 50%, with one patient remaining on protocol for 3 years.
Immunisation with the allogeneic LNCaP/IL-2/IFN-gamma vaccine is safe and feasible without any dose-limiting toxicity or autoimmunity. A 50% PSA decline was achieved in two of the six patients. This encouraging data provides the scientific rationale for further investigation of the vaccine in a phase II trial.
本疫苗研究的目的是确定用表达重组白细胞介素 -2（IL -2）和干扰素 -γ（IFN -γ）的同种异体前列腺癌细胞系LNCaP进行疫苗接种的安全性和可行性，并评估在HLA - A2匹配的激素难治性前列腺癌（HRPC）患者中诱导肿瘤特异性免疫反应的疗效。
在一项剂量递增的I期研究中，HLA - A2匹配的HRPC患者在研究第1天、15天、29天和92天接受四次经逆转录病毒转导以分泌IL -2和IFN -γ的辐照同种异体LNCaP细胞疫苗接种，随后每91天接种一次，除非有明显的肿瘤进展。
三名接受第一剂量水平（750万个细胞）的患者未出现剂量限制性毒性或包括自身免疫在内的疫苗相关不良事件。三名接受第二剂量水平（1500万个细胞）的患者中有一名在第八次接种后出现了短暂的自限性3级局部注射部位反应（溃疡）。在所有六名患者中均检测到针对多种前列腺肿瘤相关抗原的疫苗诱导免疫反应。三名接受较高剂量的患者中有两名血清前列腺特异性抗原（PSA）值下降超过50%，其中一名患者按方案治疗了3年。
用同种异体LNCaP/IL -2/IFN -γ疫苗进行免疫接种是安全可行的，没有任何剂量限制性毒性或自身免疫。六名患者中有两名实现了PSA下降50%。这些令人鼓舞的数据为在II期试验中进一步研究该疫苗提供了科学依据。
