Knight B C, Souberbielle B E, Rizzardi G P, Ball S E, Dalgleish A G
Division of Oncology, St George's Hospital Medical School, Tooting, London, UK.
Melanoma Res. 1996 Aug;6(4):299-306. doi: 10.1097/00008390-199608000-00004.
In an attempt to induce an immune response against tumour antigens, several groups are transfecting cytokine and other genes into autologous tumour cells which are given to the patient as a vaccine. This process is labour-intensive, time-consuming and expensive. Allogeneic cells would offer a more convenient vehicle for the delivery of cytokines and other molecules. However, current dogma suggests that MHC-matched cells are a prerequisite for an effective immune response. Using murine melanoma models we compared allogeneic and autologous vaccination and showed that the survival of C56BL/6 mice (H-2b) was prolonged with some degree of protection achieved against an autologous B15-F10 (H-2b) cell challenge when the mice were vaccinated with allogeneic K1735-M2 (H-2k) cells but not when immunized with autologous B16-F10 cells. Both vaccination with live and irradiated allogeneic cells induced an anti-tumour effect using only one immunization and no boost or adjuvant. Protection was not observed after vaccination with another melanoma (S91; H-2d) or with a carcinoma (A9HT; H-2k). Allogeneic vaccination promoted a cytotoxic cellular response against both the allogeneic and the syngeneic melanomas. This allogeneic vaccination model will be useful for studying the underlying mechanisms of protection, in both pre- and post-challenge settings, as well as for developing whole cell vaccination systems using genetically modified allogeneic tumour cells.
为了诱导针对肿瘤抗原的免疫反应,几个研究小组正在将细胞因子和其他基因转染到自体肿瘤细胞中,并将这些细胞作为疫苗给予患者。这个过程劳动强度大、耗时且昂贵。异基因细胞将为细胞因子和其他分子的递送提供更方便的载体。然而,目前的理论认为,MHC匹配的细胞是有效免疫反应的先决条件。我们使用小鼠黑色素瘤模型比较了异基因和自体疫苗接种,结果表明,当用异基因K1735-M2(H-2k)细胞对C56BL/6小鼠(H-2b)进行疫苗接种时,其生存期延长,并且在一定程度上对自体B15-F10(H-2b)细胞攻击具有保护作用,而用自体B16-F10细胞免疫时则没有这种保护作用。用活的和经辐照的异基因细胞进行疫苗接种,仅一次免疫即可诱导抗肿瘤作用,无需加强免疫或佐剂。用另一种黑色素瘤(S91;H-2d)或癌(A9HT;H-2k)进行疫苗接种后未观察到保护作用。异基因疫苗接种促进了针对异基因和同基因黑色素瘤的细胞毒性细胞反应。这种异基因疫苗接种模型将有助于在攻击前和攻击后的环境中研究保护的潜在机制,以及开发使用基因修饰的异基因肿瘤细胞的全细胞疫苗接种系统。