Popescu Mircea C, Robb Richard J, Batenjany Michael M, Boni Lawrence T, Neville Mary E, Pennington Robin W, Neelapu Sattva S, Kwak Larry W
XEME Biopharma, Plainsboro, NJ 08536, USA.
Blood. 2007 Jun 15;109(12):5407-10. doi: 10.1182/blood-2006-08-039446. Epub 2007 Mar 9.
Therapeutic vaccination against idiotype is a promising strategy for immunotherapy of B-cell malignancies. Its feasibility, however, is limited by the requirement for a patient-specific product. Here we describe a novel vaccine formulation prepared by simply extracting cell-membrane proteins from lymphoma cells and incorporating them together with IL-2 into proteoliposomes. The vaccine was produced in 24 hours, compared with more labor-intensive and time-consuming hybridoma or recombinant DNA methods. The vaccine elicited T-cell immunity in vivo, as demonstrated by secretion of type 1 cytokines. It protected against tumor challenge at doses of tumor antigen 50 to 100 times lower than that previously observed using either liposomes formulated with IL-2 and secreted lymphoma immunoglobulin or a prototype vaccine consisting of lymphoma immunoglobulin conjugated to keyhole limpet hemocyanin. The increased potency justifies testing similar patient-specific human vaccines prepared using extracts from primary tumor samples.
抗独特型治疗性疫苗接种是B细胞恶性肿瘤免疫治疗的一种有前景的策略。然而,其可行性受到对患者特异性产品需求的限制。在此,我们描述了一种新型疫苗制剂,它通过简单地从淋巴瘤细胞中提取细胞膜蛋白并将其与白细胞介素-2一起掺入蛋白脂质体中制备而成。与劳动强度更大、耗时更长的杂交瘤或重组DNA方法相比,该疫苗在24小时内即可生产出来。该疫苗在体内引发了T细胞免疫,这通过1型细胞因子的分泌得到证明。在肿瘤抗原剂量比先前使用含有白细胞介素-2和分泌型淋巴瘤免疫球蛋白的脂质体或由与钥孔血蓝蛋白偶联的淋巴瘤免疫球蛋白组成的原型疫苗低50至100倍的情况下,它能保护机体免受肿瘤攻击。这种增强的效力证明了对使用原发性肿瘤样本提取物制备的类似患者特异性人类疫苗进行测试的合理性。