Preservation of recall immunity in anti-CD3-treated recent onset type 1 diabetes patients

Alkemade, G.M.; Hilbrands, R.; Vandemeulebroucke, E.; Pipeleers, D.; Waldmann, H.; Mathieu, C.; Keymeulen, B.; Roep, B.O.

doi:doi:10.1002/dmrr.1273

BACKGROUND The safety of any immune modulating agent in type 1 diabetes mellitus (T1DM) involves its selectivity on autoimmunity and its preservation of recall and tumour immunity. METHODS We performed lymphocyte proliferation tests on seven recent onset diabetic patients treated with anti-CD3 (Otelixizumab; ChAglyCD3) and five recent onset diabetic patients treated with placebo, on average 2 years after therapy. RESULTS Proliferative responses towards common viral, bacterial and yeast antigens upon in vitro stimulation with a range of recall antigens in anti-CD3-treated T1DM patients were highly similar to those in placebo-treated T1DM patients. Similarly, T-cell responses towards autoantigens were equally low between the two groups, several years after diagnosis of T1DM. The proliferative response upon stimulation with the human suppressor protein p53 was invariably high in both anti-CD3- and placebo-treated patients, implying preserved anti-tumour immunity in anti-CD3 treatment....Show moreBACKGROUND The safety of any immune modulating agent in type 1 diabetes mellitus (T1DM) involves its selectivity on autoimmunity and its preservation of recall and tumour immunity. METHODS We performed lymphocyte proliferation tests on seven recent onset diabetic patients treated with anti-CD3 (Otelixizumab; ChAglyCD3) and five recent onset diabetic patients treated with placebo, on average 2 years after therapy. RESULTS Proliferative responses towards common viral, bacterial and yeast antigens upon in vitro stimulation with a range of recall antigens in anti-CD3-treated T1DM patients were highly similar to those in placebo-treated T1DM patients. Similarly, T-cell responses towards autoantigens were equally low between the two groups, several years after diagnosis of T1DM. The proliferative response upon stimulation with the human suppressor protein p53 was invariably high in both anti-CD3- and placebo-treated patients, implying preserved anti-tumour immunity in anti-CD3 treatment. CONCLUSIONS As long-term focus on side effects is key, we demonstrate in this sub-cohort of recent onset T1DM patients treated with Otelixizumab that recall immunity is preserved in spite of high-dose anti-CD3 treatment, adding to the safety of anti-CD3 treatment as an immune-modulatory agent in the treatment of T1DM.Show less

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Preservation of recall immunity in anti-CD3-treated recent onset type 1 diabetes patients