Anti-transferrin receptor monoclonal antibodies demonstrate direct anti- proliferative and cytotoxic effects on human tumor cells, and have substantial activity in experimental tumor systems. Recent early data from a Phase I trial of IgA anti-transferrin receptor antibody 42/6 showed unexpected anti-tumor activity at extremely low antibody doses. This proposal requests funds to investigate the safety of murine anti-Tf receptor monoclonal antibody 42/6 in therapy of human cancer. The trial will be accompanied by pharmacokinetic and toxicology monitoring. the 42/6 trial marks the first time a mouse IgA antibody has been given to man. Bone marrow progenitor cultures performed before and after monoclonal antibody infusions will be used to assess delivery of antibodies to this tissue and anti-proliferative effects of the antibodies on marrow cell growth. Because objective clinical responses to 42/6 were observed at extraordinarily low doses which do not result in measurable mouse antibody in serum, additional studies will investigate mechanisms of these responses. The ability of IgA 42/6 and IgG anti-Tf receptor antibodies used alone and in combination to mediate tumor cell killing by immune effector cells from patients and normal donors will be assessed.
| Kling, P J; Dragsten, P R; Roberts, R A et al. (1996) Iron deprivation increases erythropoietin production in vitro, in normal subjects and patients with malignancy. Br J Haematol 95:241-8 |
| Brooks, D; Taylor, C; Dos Santos, B et al. (1995) Phase Ia trial of murine immunoglobulin A antitransferrin receptor antibody 42/6. Clin Cancer Res 1:1259-65 |
