Immunotherapy trials: Current status and future directions with special emphasis on biologic drugs

Hollinshead, Ariel C.

doi:10.1007/bf00201907

Cited by 5 publications

(2 citation statements)

References 25 publications

(12 reference statements)

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“…The administration of naturally occurring or synthetic biological response modifiers has been reported to enhance host immune reactivity and elicit antitumor activity [11,24,28]. In patients, however, the maximum tolerated dose of immunomodulators such as interferons and interleukins is lower than that which exhibits maximum biological activity [20,21,31].…”

Section: Discussionmentioning

confidence: 99%

An assessment of the effects of swainsonine on survival of mice injected with B16-F10 melanoma cells

et al. 1990

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Systemic administration of swainsonine, an indolizidine alkaloid, inhibits the experimental metastasis of B16-F10 murine melanoma cells. This activity can be attributed primarily to swainsonine-mediated enhancement of host natural killer cell activity. As one next step towards investigating the potential therapeutic utility of this drug, its efficacy in enhancing host survival in the same B16-F10 model system has been assessed. In studies employing intravenously injected tumor cells, pretreatment of mice with swainsonine-containing drinking water provided a reproducible protective effect for the host. This prolongation of survival was substantially enhanced when swainsonine was administered in combination with either of two other immunomodulators, polyinosinic: cytidylic acid (poly-IC) or interleukin-2. In studies in which combinations of these agents were administered after intravenous injection of tumor cells, or after subcutaneous implantation, a greatly reduced effect on host survival was observed. However, when used in combination with cyclophosphamide (to block the effects of suppressor T cells), swainsonine did increase mean survival time. The implications of these results for the use of swainsonine in treatment of metastatic or localized disease, together with its potential mechanism(s) of action, are discussed.

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Section: Discussionmentioning

confidence: 99%

An assessment of the effects of swainsonine on survival of mice injected with B16-F10 melanoma cells

et al. 1990

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“…Recently immunotherapy has gained increasing interest as a treatment of cancer [5,6,9,[11][12][13]. It could be demonstrated in several animal models that active specific immunotherapy (ASI) leads to the induction of a specific antitumor response [9,10,23].…”

Section: Introductionmentioning

confidence: 99%

Postoperative active specific immunization in curatively resected colorectal cancer patients with a virus-modified autologous tumor cell vaccine

Lehner

Schlag

Liebrich

et al. 1990

Cancer Immunol Immunother

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Active specific immunotherapy was performed in a phase I study in 20 colorectal cancer patients after surgical resection of the tumor. An autologous tumor cell vaccine surface modified by Newcastle disease virus (NDV) was used, which showed the following characteristics. After mechanical and enzymatic dissociation of the tumor tissue an average of 5 x 10(7) cells/g tissue was obtained. According to trypan blue dye exclusion assay the average viability was 72%. Following irradiation (200 Gy) the inactivation of proliferative activity of the cells could be demonstrated by the absence of incorporation of 3H-labelled thymidine. The cells were, however, still metabolically active as shown by the incorporation of [3H]-uridine and a mixture of 3H-labelled amino acids. Epithelium-specific antigens (detected by mAb HEA125) were expressed on more than 75% cells of the cell suspension indicating a high amount of (epithelium-derived) tumor cells. In order to increase the immunogenicity of the tumor cells the suspended cells were infected by the nonlytic, apathogenic Ulster strain of NDV. The successful modification of tumor cells with NDV could be shown by electron microscopy. Three weeks postoperatively cells were thawed, virus-modified, and inoculated intradermally in the upper thigh. Several cell and virus concentrations were tested in each patient. As control, tumor cells without NDV, NDV alone and normal colon mucosa were used. The number of tumor cells ranged from 2 x 10(6) up to 2 x 10(7) cells and NDV concentrations from 4 to 64 hemagglutination units (HU) were tested. Sixteen patients responded with a delayed-type hypersensitivity (DTH) skin reaction to the vaccine. The best DTH reaction, measured 24 h following vaccination, was obtained using a vaccine consisting of 1 x 10(7) tumor cells and 32 HU NDV (median induration of 8 mm). Response to NDV alone was seen in 2 patients only (median induration of 3 mm); 12 patients responded to tumor cells (1 x 10(7) alone (median induration of 4 mm). Of 10 patients tested with normal colorectal mucosa, 4 responded with a median induration of 3.5 mm. DTH responses to the vaccine of 1 x 10(7) tumor cells and 32 HU NDV increased throughout the repeated vaccinations to a median induration of 9.5 mm at the end of the therapy. No severe side-effects in the course of the immunotherapy, except for mild fever in 4/20 patients, were observed. The results of our phase I study show that this type of autologous colorectal tumor cell vaccine is ready for a large clinical trial to prove its efficacy.

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Tumor Metastasis: The Possible Role of Eicosanoids

Kort

Bijma

1989

Carcinogenesis and Dietary Fat

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Immunotherapy trials: Current status and future directions with special emphasis on biologic drugs

Cited by 5 publications

References 25 publications

An assessment of the effects of swainsonine on survival of mice injected with B16-F10 melanoma cells

An assessment of the effects of swainsonine on survival of mice injected with B16-F10 melanoma cells

Postoperative active specific immunization in curatively resected colorectal cancer patients with a virus-modified autologous tumor cell vaccine

Tumor Metastasis: The Possible Role of Eicosanoids

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