Kim T S, Russell S J, Collins M K, Cohen E P
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60680.
Int J Cancer. 1993 Nov 11;55(5):865-72. doi: 10.1002/ijc.2910550528.
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-I 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.
如果用一种分泌白细胞介素-2（IL-2）的异基因细胞构建体对携带B16黑色素瘤（H-2b）的C57BL/6小鼠（H-2b）进行单独免疫治疗，该构建体表达黑色素瘤相关抗原（MAA）以及主要组织相容性复合体（MHC）I类决定簇（H-2k；RLBA-IL-2细胞），那么这些小鼠的存活期会延长。如果小鼠在注射活的B16细胞的同时或之后6天进行免疫，情况就是如此。在类似条件下，用表达MAA但不分泌IL-2的异基因细胞构建体（H-2k；RLBA-ZipNeo细胞），或用分泌IL-2但不形成MAA的异基因构建体（H-2k；LM-IL-2细胞）免疫的荷瘤小鼠的存活期也会延长。然而，在这些情况下，存活期明显短于用将IL-2分泌与MAA表达相结合的细胞构建体免疫的小鼠。用未转染的LM(TK-)细胞（H-2k）或经照射的B16细胞（H-2b）免疫的荷瘤小鼠存活期并不比未治疗的小鼠长。尽管治疗动物的存活期延长了，但在大多数情况下肿瘤生长会复发。用异基因细胞构建体治疗的小鼠复发肿瘤形成黑色素，并且在组织学上与未治疗小鼠的肿瘤无法区分。复发肿瘤的细胞对进一步的免疫治疗以及从最初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的同基因B16细胞注射到C57BL/6小鼠中总是会导致出现不分泌IL-2的黑色素瘤。在类似情况下，注射分泌IL-2或不分泌IL-2的异基因细胞构建体的C57BL/6小鼠中肿瘤未能生长。因此，异基因抗原的表达保护小鼠免受细胞免疫原的生长影响。
