Genes for IL-15 were transfected into RM-1 (prostate cancer), B16 (melonoma), and 4T1 (breast cancer) cancer cells. The transfected genes consisted of two types, one for the isoform of IL-15 which has a full length leader sequence and is secreted from the cell, and the second for the isoform of IL-15 which has a truncated leader sequence and accumulates in the cytoplasm of the cell. Both kinds of each cancer cell line were cloned, showing that there was little translation of the IL-15 genes in RM-1 and 4T1 cells, and good translation of the IL-15 genes in B16. The vaccine efficacy of the original three cancer cell lines reflected these levels of IL-15. A genetic modification of the IL-15 gene was made to remove the signal peptide of the truncated isoform to make a very short sequence peptide (VSSP-1). The translation of the new genetically modified IL-15 gene was determined by cloning it into all of the cell lines, where it was found to give greater translation of IL-15. The vaccine efficacy for the various IL-15 transfectants of B16 melanoma was determined in mouse tumor studies. The VSSP-1 transfected B16 melanoma vaccine was the most efficacious.
Additional contributor: W. Robert Fleischmann, Jr. (faculty mentor).
Comparative Efficacy Study of IL-15 Transfections in Various Mouse Cancer Cells (RM-1 Prostate Cancer, B16 Melanoma, and 4T1 Breast Cancer).
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