Antibody responses to macrocycles in lymphoma

Area of Science:

• Immunology
• Radiochemistry
• Oncology

Background:

• Metallic radioimmunoconjugates are promising for cancer imaging and therapy.
• Macrocyclic chelating agents form stable conjugates but may be immunogenic.
• Assessing human antibody responses to macrocyclic chelators in radiolabeled Lym-1 is crucial.

Purpose of the Study:

• To evaluate human antibody responses in patients treated with Lym-1 radiolabeled with macrocyclic chelators 1,4,8,11-tetraazacyclotetradecane-N,N',N",N"'-tetraacetic acid (TETA) or 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA).
• To compare the immunogenicity of macrocyclic chelators versus other radiometal chelating agents.

Main Methods:

• 18 patients with lymphocytic malignancies received 67Cu-2IT-BAT-Lym-1 or 111In-2IT-BAD-Lym-1.
• Solid-phase ELISA was used to detect antibodies against Lym-1, DOTA, TETA, or 2IT moieties.
• Antibody responses were quantified in relation to the chelating agents and the Lym-1 antibody.

Main Results:

• No patients developed serum sickness.
• No antibodies to Lym-1 or DOTA were detected in patients receiving 111In-2IT-BAD-Lym-1.
• Two patients (15%) receiving 67Cu-2IT-BAT-Lym-1 developed antibodies to TETA and Lym-1; one developed antibodies to Lym-1 only. No patient developed antibodies solely against the macrocycle or the 2IT molecule.

Conclusions:

• Macrocycles like DOTA and TETA can be haptens and potentially immunogenic.
• Findings do not support the view that macrocycles are inherently more immunogenic than other radiometal chelating agents.
• The immunogenicity of macrocyclic chelators in radioimmunoconjugates requires careful consideration but may not be greater than other agents.