Interleukin 2‐dependent activation of tumor‐specific cytotoxic T lymphocytes <i>in vivo</i>

Ley, Victoria; Langlade‐Demoyen, Pierre; Kourilsky, Philippe; Larsson-Sciard, Eva-Lotta

doi:10.1002/eji.1830210350

Cited by 74 publications

(26 citation statements)

References 18 publications

(2 reference statements)

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“…When the IL-2, or IL-4-secreting cells were present in a 10-fold excess, initial delay in the growth of the unmodified cells was observed, but rapidly growing tumours eventually formed in all animals ( Figure 3). These data are in contrast to several previous studies, which have demonstrated effective induction of parental tumour rejection by admixture of 50% IL-2 Ley et al, 1991), or IL-4-secreting cells (Tepper et al, 1989;Golumbek et al, 1991).…”

Section: Methodscontrasting

confidence: 99%

“…However, another report describes a complete absence of induction of protection by IL-4-secreting plasmacytoma cells (Tepper et al, 1992). Two reports described lasting protection induced by IL-2-secreting cells Ley et al, 1991), the work of Ley et al (Ley et al, 1991) demonstrated an enhanced protection compared to parental mastocytoma cells. The study of Fearon et al described short-term protection induced by IL-2-secreting colon tumour cells which is greatly diminished after 28 days (Fearon et al, 1990).…”

Section: Methodsmentioning

confidence: 99%

“…As gene delivery to all cells within a tumour will probably not be feasible, cytokine secretion by some cells within a tumour would have to lead to the rejection of adjacent, unmodified cells for direct cytokine gene delivery to be effective. An effect on the rejection of admixed, unmodified cells has been reported for IL-2 Ley et al, 1991;), IL-4 (Tepper et al, 1989;Golumbek et al, 1991) and TNF-a (Asher et al, 1991)-secreting rodent tumour cells.…”

mentioning

confidence: 95%

“…Secretion of IL-2 (Fearon et al, 1990;Russell et al, 1991;Ley et al, 1991), (Tepper et al, 1989;Golumbek et al, 1991), y-interferon ('y-IFN) (Watanabe et al, 1989;Esumi et al, 1991), tumour necrosis factor-a (TNF-a) (Asher et al, 1991;Blankenstein et al, 1991), granulocyte colony stimulating factor (Colombo et al, 1991), or interleukin 7 (Hock et al, 1991;McBride et al, 1992) (Miller, 1992). As gene delivery to all cells within a tumour will probably not be feasible, cytokine secretion by some cells within a tumour would have to lead to the rejection of adjacent, unmodified cells for direct cytokine gene delivery to be effective.…”

mentioning

confidence: 99%

“…Another human gene therapy trial is employing this approach with IL-2 and TNF-a-secreting tumour cells (Rosenberg et al, 1992a;Rosenberg, 1992b). In rodent tumour studies IL-2 Ley et al, 1991), (Golumbek et al, 1991) and y-IFN (Watanabe et al, 1989;)-secreting tumour cells have each been shown to induce protection against parental tumour cell challenge. In order to determine which of these therapeutic routes might be the more feasible, we have compared the properties of IL-2 and IL-4-secreting tumour cells in a single murine tumour, the transplantable fibrosarcoma, FS29 (Eccles et al, 1980).…”

mentioning

confidence: 99%

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Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour

Patel

Flemming²,

Russell³

et al. 1993

Br J Cancer

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Summary Engineering of a variety of rodent tumour cells to secrete either interleukin 2 (IL-2), or interleukin 4 (IL-4), has been demonstrated to reduce their tumorigenicity. However the mechanisms of action of secreted IL-2 and IL-4 have not been compared in a single rodent tumour. Here we demonstrate that the weakly immunogenic murine fibrosarcoma FS29 had reduced growth rate and in some cases was rejected by syngeneic animals, when modified to secrete either IL-2 or IL-4, but not IL-5. Immunohistochemical analysis of tumour nodules undergoing regression showed stimulation of a largely lymphocytic infiltrate by IL-2 and a macrophage and granulocyte infiltrate, with a small number of lymphocytes by IL-4. Indeed, secretion of low levels of IL-2 and IL-4 in combination resulted in optimal rejection, suggesting that the two cytokines might mobilise different and complementary effector cell mechanisms. Both IL-2 and IL-4-secreting cells failed to induce the rejection of admixed, unmodified FS29 cells. The loss of cytokine secreting cells from such admixtures occurred more rapidly for IL-2-secreting cells. Injection of IL-4-secreting, but not IL-2-secreting FS29 cells could protect mice from a delayed challenge with unmodified FS29 cells. These data suggest that IL-4 secretion stimulates the better long-term host anti-tumour response.

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Section: Methodscontrasting

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 95%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour

Patel

Flemming²,

Russell³

et al. 1993

Br J Cancer

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Induction of CD8 molecules on thymic γ/δ T cells in vitro is dependent upon α/β T cells

1991

Self Cite

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Thymocytes differentiate upon interactions with microenvironmental components, but the precise role of different stromal cells, or other T cells, in early differentiative events remains unclear. Here we have analyzed the in vitro differentiation of double-negative (DN) thymocytes from young adult mice. We demonstrate that a substantial proportion of DN thymocytes differentiate into CD8+ gamma/delta T cells upon stimulation with concanavalin A and recombinant interleukin 2. However, if alpha/beta T cells are excluded from the initial population of DN thymocytes, the CD8+ gamma/delta T cells do not appear in the cultures. These results suggest a role for T-T cell interactions in thymic differentiative events, and provide evidence for physiological interactions between the alpha/beta and gamma/delta T cell compartments within the thymus.

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Experimental gene therapy of cancer using tumor cells engineered to secrete interleukin‐13

et al. 1995

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Cytokines locally delivered to the site of a tumor boost both specific and nonspecific host anti-tumor defenses. Interleukin (IL)-13 is a recently described cytokine produced by mouse type 2 helper T lymphocytes. The aim of this study was to evaluate the inhibition of tumor growth induced by IL-13 delivered locally within or around transplanted tumor cells in mice. We observed that local administration of IL-13 at the site of transplanted tumor cells in vivo had potent inhibitory effects on growth of both immunogenic (P815 mastocytoma, H-2d) or nonimmunogenic (3LL lung carcinoma, H-2b) tumor cells. Mice injected with transfected P815 cells secreting large amounts of IL-13 rejected the P815 tumor and developed systemic specific anti-tumor immunity leading to long-lasting specific anti-tumor protection. Less efficient anti-tumoral effects were obtained with the nonimmunogenic 3LL tumor model when local administration of IL-13 was achieved by co-inoculating xenogeneic chinese hamster ovary (CHO) IL-13 cells. Several local injections of CHO IL-13 cells were needed to obtain rejection of 3LL tumors and no induction of long-lasting anti-3LL memory was obtained. Several studies were performed to elucidate the IL-13 anti-tumoral effects. Experiments with nude mice indicated that Il-13 can also stimulate nonspecific anti-tumor defenses. The histological examination of P815 IL-13 cells undergoing rejection showed monocytic cells and neutrophils infiltrating the tumor. Studies indicated that IL-13 administered in vitro did not directly stimulate the cytotoxicity of peritoneal macrophages and natural killer cells. However, experiments with Boyden chemotaxis chambers indicated that IL-13 was chemotactic for macrophages. Finally, preliminary experiments in vitro suggest that IL-13 improved antigenic presentation of P815 membranes. Thus, anti-tumor effects of IL-13 in vivo most probably result from pleiotropic effects including recruitment of nonspecific cells and improved stimulation of immune-specific anti-tumor effectors.

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Interleukin 2‐dependent activation of tumor‐specific cytotoxic T lymphocytes in vivo

Cited by 74 publications

References 18 publications

Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour

Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour

Induction of CD8 molecules on thymic γ/δ T cells in vitro is dependent upon α/β T cells

Experimental gene therapy of cancer using tumor cells engineered to secrete interleukin‐13

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