Immunization with interleukin-2-secreting allogeneic mouse fibroblasts expressing melanoma-associated antigens prolongs the survival of mice with melanoma.
Immunization with interleukin-2-secreting allogeneic mouse fibroblasts expressing melanoma-associated antigens prolongs the survival of mice with melanoma.
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使用表达黑色素瘤相关抗原的分泌白细胞介素2的同种异体小鼠成纤维细胞进行免疫可延长患有黑色素瘤的小鼠的存活时间。
DOI：
10.1002/ijc.2910550528
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发表时间：
1993
影响因子：
6.4
通讯作者：
Cohen,EP
中科院分区：
文献类型：
--
作者：
Kim,TS;Russell,SJ;Collins,MK;Cohen,EP
携带B16黑色素瘤（H‐2b）的C57BL/6小鼠（H‐2b）如果仅通过分泌白细胞介素- 2 （IL‐2）的异基因细胞构建体免疫治疗，其表达黑色素瘤相关抗原（MAA）以及主要组织相容性复合体（MHC）类决定因子（H‐2k； RLBA‐IL‐2细胞），则可以延长存活时间。如果小鼠同时免疫，或6天后注射活的B16细胞，情况就是这样。在类似的条件下，用表达MAA但不分泌IL - 2的同种异体细胞结构（H‐2k） （RLBA‐ZipNeo细胞）或分泌IL - 2但不形成MAA的同种异体细胞结构（H‐2k）免疫的荷瘤小鼠的存活时间也延长了。然而，在这些情况下，生存期明显短于结合IL - 2分泌和MAA表达的细胞构建免疫的小鼠。用未转染的LM（TK‐）细胞（H‐2k）或辐照的B16细胞（H‐2b）免疫的荷瘤小鼠比未转染的小鼠存活时间更长。虽然接受治疗的动物的生存时间延长了，但在大多数情况下，肿瘤又复发了。用同种异体细胞结构治疗的小鼠的复发肿瘤形成黑色素，在组织学上与未治疗的小鼠的肿瘤没有区别。来自复发肿瘤的细胞对进一步的免疫治疗和从最初使用相同细胞免疫原免疫的小鼠脾脏中获得的细胞毒性效应细胞具有抗性。将分泌IL - 2的同源B16细胞注射到C57BL/6小鼠体内，不可避免地导致非分泌IL - 2的黑色素瘤的出现。在类似的情况下，注射分泌IL - 2或不分泌IL - 2的同种异体细胞构建物的C57BL/6小鼠，肿瘤未能发展。因此，异体抗原的表达保护小鼠免受细胞免疫原的生长。
The survival of C57BL/6 mice (H‐2b) bearing B16 melanoma (H‐2b) was prolonged if the animals were treated solely by immunization with an interleukin‐2 (IL‐2)‐secreting allogeneic cell construct that expressed melanoma‐associated antigens (MAA) along with major histocompatibility complex (MHC) class‐l determinants (H‐2k; RLBA‐IL‐2 cells). This was the case if the mice were immunized simultaneously with, or 6 days following, the injection of viable B16 cells. Under similar conditions, the survival of tumor‐bearing mice immunized with an allogeneic cell construct (H‐2k) that expressed MAA but did not secrete IL‐2 (RLBA‐ZipNeo cells), or with an allogeneic construct (H‐2k) that secreted IL‐2 but did not form MAA (LM‐IL‐2 cells), was also prolonged. However, in these instances, the period of survival was significantly shorter than that of mice immunized with the cell construct that combined IL‐2 secretion with the expression of MAA. Tumor‐bearing mice immunized with non‐transfected LM(TK‐) cells (H‐2k), or irradiated B16 cells (H‐2b) failed to survive longer than untreated mice. Although the survival of the treated animals was prolonged, in most instances tumor growth recurred. The recurrent tumors in mice treated with the allogeneic cell constructs formed melanin and were histologically indistinguishable from tumors in untreated mice. Cells from the recurrent tumors were resistant to further immunotherapy and to cytotoxic effector cells obtained from the spleens of mice immunized with the same cellular immunogen used initially. The injection of IL‐2‐secreting syngeneic B16 cells into C57BL/6 mice invariably resulted in the appearance of non‐IL‐2‐secreting melanomas. Under similar circumstances, tumors failed to develop in C57BL/6 mice injected with IL‐2‐secreting, or non‐secreting, allogeneic cell constructs. Thus, the expression of allogeneic antigens protected the mice from growth of the cellular immunogens.