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Figure 19.36 Diagrammatic model of immunotherapeutic interaction of LAK cells and TIL on a target neoplasm. TIL and LAK cells are obtained from the autologous neoplasm and peripheral blood of the patient, expanded as described above, and then reinoculated into the patient in the presence of interleukin-2 administered simultaneously. On the left, TIL are removed from fresh neoplasm obtained at surgery from the patient, expanded, and then reinfused together with interleukin-2 with subsequent reinfiltration of the target neoplasm. On the right, NK and T cells in peripheral blood are removed from leukapheresis and the LAK cells after expansion infused into the patient along with interleukin-2, many of the cells returning to the neoplasm where they in turn produce interferon-y (IFN) and tumor necrosis factor (TNF). (Adapted from Atzpodien and Kirchner, 1990, with permission of the authors and publisher.)

Figure 19.36 Diagrammatic model of immunotherapeutic interaction of LAK cells and TIL on a target neoplasm. TIL and LAK cells are obtained from the autologous neoplasm and peripheral blood of the patient, expanded as described above, and then reinoculated into the patient in the presence of interleukin-2 administered simultaneously. On the left, TIL are removed from fresh neoplasm obtained at surgery from the patient, expanded, and then reinfused together with interleukin-2 with subsequent reinfiltration of the target neoplasm. On the right, NK and T cells in peripheral blood are removed from leukapheresis and the LAK cells after expansion infused into the patient along with interleukin-2, many of the cells returning to the neoplasm where they in turn produce interferon-y (IFN) and tumor necrosis factor (TNF). (Adapted from Atzpodien and Kirchner, 1990, with permission of the authors and publisher.)

of up to 40% have been seen (Oleksowicz and Dutcher, 1999) in metastatic renal cell carcinoma, while only a 13% response may be seen in the therapy of melanoma by IL-2 (cf. Bishop, 1996). IL-2 therapy, like a number of other immunotherapies, also has profound toxic effects in patients, probably because its effects are far more diverse than simply those of NK cells (Janssen et al., 1994). It should be noted that in a very small percentage of cases, 6% to 15% (Figlin et al., 1997; Oleksowicz and Dutcher, 1999), a complete remission was achieved, which remained for a number of years or as long as the study continued. Such effects are reminiscent of the "spontaneous" disappearance of neoplasms with no obvious explanation. The difficulty is determining the exact conditions within the individual that give rise to such complete responses. In addition to IL-2, IL-12 (Okuno et al., 1996) and IL-10 (Kundu and Fulton, 1997) have shown significant immunotherapeutic effects in both human and experimental situations.

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