Immunotherapeutic Properties of Recombinant Lymphokines in the Treatment of Metastatic Disease

Difference in cytotoxicity against hepatocellular carcinoma between liver and periphery natural killer cells in humans

“…[5][6][7][8][9] Despite these promising advances, the systemic administration of cytokines such as IL-2, that nonspecifically activate a broad range of different immune cell types, is associated with significant toxicity. 5,10 The adoptive transfer of NK cells further demonstrates the ability of NK cells to mount a therapeutic anti-tumor response and suggests that NK cells can be used in controlling human malignancy. 11,12 In these studies, autologous or even haploidentical lymphokine-activated killer cells obtained from peripheral blood mononuclear cells (PBMCs) have been administered to patients, although their comprehensive role in the treatment of selected malignancies remains to be elucidated.…”

Antibody-Cytokine Fusion Proteins for the Therapy of Breast Cancer

“…Cells: 38C13 is a C3H/HeN murine B cell lymphoma expressing a surface |XK antibody (Id) that arose in a carcinogen (7,12-dimethylbenz(a)anthracene) treated mouse (20,21). VI is an Id-negative variant derived from the original 38C13 tumor (22).…”

“…IL-2 induces the proliferation of T cells, supports the growth of Ag-specific T cell clones, and enhances the activity of T and NK cells (21). Fusion of IL-2 to Abs specific for tumor-associated Ags such as ganglioside GD2 and the Id of a murine lymphoma has resulted in fusion proteins that have shown much promise as agents for stimulating tumorspecific immune responses (22)(23)(24)(25)(26)(27).…”

“…GM-CSF is a cytokine associated with the growth and differentiation of hematopoietic cells. It is also a potent immunostimulator with pleiotropic effects, including the augmentation of antigen presentation in a variety of cells (17)(18)(19)(20)(21)(22), increased expression of MHC class II on monocytes and adhesion molecules on granulocytes and monocytes (23)(24)(25), and amplification of T-cell proliferation (26). In animals, the injection of GM-CSF potentiates the protective effects of an anti-tumor vaccine by enhancing Tcell immunity (26) and vaccination with GM-CSF-transduced cells has been shown to be effective in the treatment of experimental tumors in murine models (27)(28)(29)(30).…”

Antibody–cytokine fusion proteins: applications in cancer therapy

“…This antibody-(IL-2) fusion protein exhibited approximately fourfold higher affinity than recombinant human IL-2 (rhIL-2) for the α -subunit of the high-affinity IL-2 receptor, and was significantly more effective in the generation of LAK cell activity compared with IL-2 alone [60]. In addition, the half-life of this antibody-(IL-2) fusion protein injected intraperitoneally in mice is 7 h [64], which is more than one order of magnitude longer than that of free IL-2 [65] but shorter than that of IgG3 alone [64]. A similar increase in half-life of IL-2 fused to an antibody was also described using an anti-Id IgG3-(IL-2) fusion protein, which recognizes the idiotype (Id) of the immunoglobulin expressed on the surface of the malignant murine 38C13 B-cell lymphoma cell line [57].…”