Antibody in Combination with Cytokines

While cytokines can induce proliferation and activation of effector cells, in the absence of cytophilic MAb, they lack tumor selectivity. Antibody-dependent cellular cytotoxicity (ADCC) is greatly augmented in vitro by cytokines (Kushner and Cheung 1989; Munn and Cheung 1987; Hank et al. 1990; Barker and Reisfeld 1993). Clinical trials of anti-NB antibody combined with GM-CSF (Ozkaynak et al. 2000; Kushner et al. 2001) or combined with IL-2 (Sondel and Hank 1997; Frost et al. 1997) have shown modest antitumor effects. While large tumor masses rarely responded to these combinations, microscopic marrow disease showed consistent response in over 50% of patients whether measured by conventional histology (Kushner et al. 2001) or by RT-PCR (Cheung et al. 2003b). In addition, response may translate into improved survival (Cheung et al. 1998a, 2003b). To prospectively evaluate the clinical efficacy of antibody in combination with cytokine therapy, ch14.18 is being tested in combination with GM-CSF and IL-2 following autologous stem-cell transplant in a phase-III U.S. Children's Oncology Group (COG) randomized trial (A. Yu et al., unpublished results).

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