Immunity to melanoma in mice immunized with transfected allogeneic mouse fibroblasts expressing melanoma-associated antigens

Kim, Young Sang; Słomski, Ryszard; Cohen, Edward P.

doi:10.1007/bf01742307

Cited by 6 publications

(9 citation statements)

References 28 publications

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“…Allogeneic tumour cells vaccines have been investigated in pre-clinical models by several groups [13][14][15][16][17][18] with the finding that vaccination with completely allogeneic vaccine cells can induce a protective response against a subsequent challenge with live autologous tumour cells. So far the only evidence of T cell involvement in the response induced by the allogeneic vaccination was by in vitro CTL data [14][15][16] with the exception of Ashley and colleagues 13 who also demonstrated, as in the present study, that an allogeneic cell line (a pre-B cell line, 300.19), modified to express a specific model antigen (human epidermal growth factor receptor variant (EGFRvIII)), mediated anti-tumour activity against intracranial established tumours also expressing the model antigen (B16-F10 melanoma and 560 astrocytoma) through both CD4+ve and CD8+ve T cells.…”

Section: Discussionmentioning

confidence: 99%

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Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

et al. 1999

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Section: Discussionmentioning

confidence: 99%

“…12 There are now several reports of allogeneic vaccine efficacy in animal models. [13][14][15][16][17][18] Morton and colleagues 19 have transferred this strategy to the clinic using unmodified allogeneic cells. However, early reports of allogeneic vaccines modified to secrete IL-2 have reported a limited response.…”

Section: Introductionmentioning

confidence: 99%

Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

et al. 1999

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“…The results (not presented) indicate that the intensity of immunofluorescent staining using polyclonal B16 antibodies raised in C57BL/6 mice (Kim et al,, 1991) was equivalent in each treatment group to that of non-selected B16 cells.…”

Section: Recurrent Melanoma Cells From Mice Immunized With Rlba-il-2 mentioning

confidence: 74%

Immunization with interleukin‐2‐secreting allogeneic mouse fibroblasts expressing melanoma‐associated antigens prolongs the survival of mice with melanoma

Kim

Russell

Collins

et al. 1993

Intl Journal of Cancer

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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.

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“…The antibodies were reactive with B16 cells, but did not react with a wide variety of nonneoplastic cells from C57BLI6J mice (Kim et al, 1991). Whether or not these determinants, or their crossreacting derivatives, were the same as those recognized in the cellular immune responses that followed immunization with the cell construct was not determined.…”

Section: Discussionmentioning

confidence: 96%

“…All the mice were exsanguinatcd 6 wecks after the last injection and the sera were pooled. The ascitic fluid and sera reacted with B16 cells, but failed to react with a variety of organs and tissues from C57BLi6.l mice (Kim et al, 1991).…”

Section: Antiseramentioning

confidence: 98%

Immunity to B16 melanoma in mice immunized with IL‐2‐secreting allogeneic mouse fibroblasts expressing melanoma‐associated antigens

Kim

Russell

Collins

et al. 1992

Intl Journal of Cancer

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Co-presentation of weak tumour-associated antigens along with strongly immunogenic determinants leads to the development of an anti-tumour immune response in recipients syngeneic with the tumour. Tumour immunity develops in mice immunized with tumour cells modified by the introduction of cDNA for interleukin-2 (IL-2). Here, we report the anti-tumour response following immunization with an IL-2-secreting cell construct that expresses tumour-associated antigens, along with allogeneic major histocompatibility antigens. The construct was prepared by transfecting LM(TK-) mouse fibroblasts (H-2k) with genomic DNA from B16 melanoma cells syngeneic in C57BL/6J mice (H-2b). Transfectants expressing melanoma-associated antigens (MAA) were then infected with an expression-competent retroviral vector containing a cDNA specifying human IL-2. Cytotoxicity toward B16 cells was detected for as long as 5 months in both spleen and macrophage cell populations in C57BL/6J mice immunized with the IL-2-secreting cells. Mice immunized with non-IL-2-secreting, MAA-positive allogeneic cells developed melanoma immunity as well, but to a lesser extent. Immunity to 2 tumour-cell lines expressing the H-2d haplotype and to YAC-1 cells was detected in peritoneal macrophages, but not in spleen cells from C57BL/6J mice immunized with the cell construct, indicating that the response to B16 cells was only partially specific. C57BL/6J mice immunized with the IL-2-secreting cell construct survived significantly longer, following an injection of viable B16 cells, than mice in various control groups. The contribution of allogeneic antigens to the melanoma immunity was indicated by the failure of mice syngeneic with LM(TK-) cells to develop melanoma immunity following immunization with non-IL-2-secreting, MAA-positive cell constructs. The formation of IL-2 partially compensated for the lack of allogeneic antigens.

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Immunity to melanoma in mice immunized with transfected allogeneic mouse fibroblasts expressing melanoma-associated antigens

Cited by 6 publications

References 28 publications

Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

Immunization with interleukin‐2‐secreting allogeneic mouse fibroblasts expressing melanoma‐associated antigens prolongs the survival of mice with melanoma

Immunity to B16 melanoma in mice immunized with IL‐2‐secreting allogeneic mouse fibroblasts expressing melanoma‐associated antigens

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