Anti-chelate antibodies after intraperitoneal yttrium-90-labeled monoclonal antibody immunoconjugates for ovarian cancer therapy.
The development of stable chelating agents for metal isotopes (e.g., 90Y) such as CITC-DTPA, a benzyl-analog of DTPA, allowed us to evaluate the efficacy of 90Y-labeled HMFG1 MAb administered intraperitoneally in patients with ovarian cancer. Our previous studies of 90Y-HMFG1 antibody, however, showed that all patients developed anti-chelate antibody responses (to the macrocycle benzyl-DOTA), resulting in clinical side effects in a significant percentage of this group.


METHODS
We evaluated the immunogenicity of CITC-DTPA (administered to 12 patients as 90Y-HMFG1-CITC-DTPA after coupling it to HSA using solid-phase ELISA.


RESULTS
Eleven of 12 evaluable patients developed anti-CITC-DTPA antibodies. Five patients (approximately 40%) developed hypersensitivity syndrome, most likely due to a type III immune reaction (serum sickness). Most patients had a low titer of pre-existing anti-chelate response which correlated positively with post-therapy response levels (p = 0.001). IgM anti-CITC-DTPA antibodies developed 2 wk while IgG antibodies developed 3 wk after treatment. Western blot analysis of post-therapy sera revealed a reaction with HSA-CITC-DTPA (60 kDa band) and no reaction with HSA or HSA-DTPA, whereas pre-therapy sera of the same patients were negative to all antigens.


CONCLUSIONS
CITC-DTPA is immunogenic in patients after intraperitoneal administration of 90Y-CITC-DTPA labeled MAbs. Self-limiting clinical side effects consistent with a serum sickness-like immune reaction were observed in 5 of 12 patients.
Kosmas
C
C
Imperial Cancer Research Fund Oncology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
Maraveyas
A
A
Gooden
C S
CS
Snook
D
D
Epenetos
A A
AA
D000906:Antibodies / Q000032:analysis*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D010051:Ovarian Neoplasms / Q000532:radiotherapy*; D004369:Pentetic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016499:Radioimmunotherapy; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use
D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015021:Yttrium Radioisotopes; D004369:Pentetic Acid