The cellular immunotherapy of cancer: Current and potential uses of interleukin-2

Increased expression of the interleukin 2 (IL-2) receptor beta chain (p70) on CD56+ natural killer cells after in vivo IL-2 therapy: p70 expression does not alone predict the level of intermediate affinity IL-2 binding.

“…The exposure of heterogeneous populations of lymphocytes to high concentrations of IIr2 activates a non-MHCrestricted cytolytic activity due to the expansion of a population of large granular lymphocytes with properties of activated NK cells (36)(37)(38) . The cells mediating this lymphokine activated killer activity effectively lyse fresh tumor targets as well as various NK-resistant cultured tumor cell lines (38) .…”

“…The functional role of these distinct NK cell subsets is also unclear, although it has been suggested that the CD16 -CD566 °ghc subset bearing the high affinity IL2R may represent a precursor population capable of expanding and differentiating in response to low physiologic concentrations of 11,2 that occur naturally in vivo (34,35) . This hypothesis is also attractive with regard to the in vivo immune activation observed in patients who have achieved steady-state serum IL2 levels of -30 U/ml during continuous infusions of 11,2 for the treatment of cancer (36) . The exposure of heterogeneous populations of lymphocytes to high concentrations of IIr2 activates a non-MHCrestricted cytolytic activity due to the expansion of a population of large granular lymphocytes with properties of activated NK cells (36)(37)(38) .…”

Effect of combined adoptive immunotherapy and radiotherapy on tumor growth

“…The successful development of this response requires specific antigen recognition and presentation, effector cell activation/differentiation, the secretion of cytokines, such as IL-2, interferon-␥ (IFN-␥), IL-1, IL-4, tumor necrosis factor ␣ and ␤ (TNF-␣ and ␤), and the development of an inflammatory phase [16]. Studies on primary human head and neck squamous cell carcinomas have shown that the inflammatory cell infiltrates seen at the tumor margins and in the stroma and parenchyma of the tumors are composed of CD8 + and CD4 + T lymphocytes, B lymphocytes, some plasma cells, NK cells, monocytes/ macrophages, and granulocytes [3,17,18].…”

Human melanoma therapy in the SCID mouse:In vivo targeting and reactivation of melanoma-specific cytotoxic T cells by bi-specific antibody fragments

“…Single bi-specific antibodies have been shown to be efficient in targeting, but cannot provide the complete signal required for T-cell activation (Becker et al, 1996). Initial trials to overcome the deficiency in co-stimulatory factors by co-administration of IL-2 have been burdened by severe side effects (Sondel et al, 1989). Pre-clinical trials with a set of 2 bi-specific antibodies have demonstrated convincing therapeutic effects.…”

“…It became obvious that the transferred lymphocytes rapidly sequestered in the spleen (Economou et al, 1996), partly because of the loss of appropriate homing molecules, partly because of a lack of co-stimulatory molecules and factors required to maintain a status of activation (Nakajima et al, 1994). Trials to circumvent the rapid decline in effector activity by the systemic application of IL-2 were frequently accompanied by severe side effects in the patient (Sondel et al, 1989). Furthermore, the support with cytokines could not cope with the problem of effector-cell targeting.…”