Preclinical evaluation of chimeric L6 antibody for the treatment of Kaposi's sarcoma with radioimmunotherapy.
L6 is a murine IgG2a monoclonal antibody with panadenocarcinoma reactivity. Chimeric L6 (ChL6), the variable region of murine L6 combined with a human IgG1 constant region, has been used in clinical trials for the delivery of radioimmunotherapy to patients with breast cancer. AIDS-associated Kaposi's sarcoma (KS), a malignancy of vascular endothelium, may be an excellent candidate for systemic radioimmunotherapy because KS is well vascularized and radioresponsive. Because ChL6 has been noted to bind vascular endothelium, our hypothesis was that ChL6 will recognize and bind KS tumors making this a potentially useful antibody for the treatment of KS with radioimmunotherapy. To test this hypothesis, 4 human KS spindle cell cultures established from cutaneous punch biopsy specimens (KS-MR, KS-NO, KS-JD and KS 6-3E) and one well-characterized human KS cell line (KS Y-1) were assessed for L6 immunoreactivity. All 5 cell cultures were L6 positive by immunohistochemistry. KS Y-1 cells grown as nude mouse xenografts were also L6 positive by immunohistochemistry. Competitive binding assays performed on the KS Y-1 and KS 6-3E cell cultures showed high density and high affinity cell binding. Biodistribution experiments performed on nude mice with KS Y-1 xenografts demonstrate tumor targeting by ChL6. These findings indicate that ChL6 may be a useful antibody for the radioimmunotherapy of KS. Future experiments will assess the therapeutic efficacy of radiolabeled ChL6 with and without concurrent systemic radiosensitizing chemotherapy.
Leigh
B R
BR
Department of Radiation Oncology, University of California, Davis, Medical Center, Sacramento 95817, USA. bryan.leigh@ucdmc.ucavis.edu
Burke
P A
PA
Hong
A M
AM
O'Donnell
R T
RT
Howell
L P
LP
Miers
L A
LA
DeNardo
G L
GL
DeNardo
S J
SJ
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D001667:Binding, Competitive; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016499:Radioimmunotherapy; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012514:Sarcoma, Kaposi / Q000532:radiotherapy*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins