Cancer vaccines: the interleukin 2 dosage effect.

Abstract:

:Cancer vaccines genetically engineered to produce interleukin 2 have been investigated intensively in a series of animal models and are at the point of entering into clinical trials. In this study we demonstrate a strong correlation between the rate of interleukin 2 production and the protection efficiency of murine S91 melanoma cell (clone M-3) vaccines. Best immunization is achieved with vaccines producing medium interleukin 2 levels of 1000-3000 units per 10(5) cells per day. Reduced interleukin 2 production evokes a corresponding decline in the number of successfully treated animals. Unexpectedly, when interleukin 2 expression is raised to high levels of 5000-7500 units per 10(5) cells per day, protection is completely absent because of impaired generation of tumor-specific cytotoxic T lymphocytes. In comparison, granulocyte-macrophage colony-stimulating factor as immunomodulator induces substantial immunization even at a moderate level of secretion and protects all animals at the maximal obtainable level of secretion. Our findings demonstrate the importance of the interleukin 2 level produced by genetically modified tumor cells and may have substantial impact for the clinical application of cancer vaccines.

authors

Schmidt W,Schweighoffer T,Herbst E,Maass G,Berger M,Schilcher F,Schaffner G,Birnstiel ML

doi

10.1073/pnas.92.10.4711

subject

Has Abstract

pub_date

1995-05-09 00:00:00

pages

4711-4

issue

10

eissn

0027-8424

issn

1091-6490

journal_volume

92

pub_type

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