Tissue distribution and serum kinetics of T101 monoclonal antibody during passive anti-cancer therapy.
We have administered fifty-six 24 hr infusions of the anti-human T-cell monoclonal antibody T101 to 10 patients with cutaneous T-cell lymphoma (CTCL) and 6 patients with chronic lymphocytic leukemia (CLL) in doses of 10, 50, 100, 150, and 500 mg. The larger doses of T101 resulted in higher, more persistent serum T101 concentrations, and CTCL patients generally developed higher serum T101 levels than CLL patients given equivalent doses. The presence of host anti-mIgG antibodies prior to infusion was associated with decreased serum concentrations of T101. Treatments that demonstrated measurable serum T101 levels were also associated with in vivo T101 binding and cytodestruction of circulating target cells. Immunofluorescence analysis of bone marrow and lymph node biopsies in CLL, and skin biopsies in CTCL, suggested that T101 had reached extravascular tumor sites. Infusion of 111In-conjugated T101 showed uptake in the liver, spleen, lymph nodes, and (in CTCL) skin infiltrates. Our data demonstrate the tissue distribution of T101 and suggest that immunoconjugates of T101 with toxins, drugs, or radioisotopes may result in better therapeutic responses.
D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007204:Indium / Q000008:administration & dosage / Q000627:therapeutic use; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000628:therapy*; D008223:Lymphoma / Q000628:therapy*; D009360:Neoplastic Cells, Circulating; D011868:Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use; D012751:Sezary Syndrome / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D011868:Radioisotopes; D007204:Indium