To determine (1) whether subcutaneous versus intravenous administration of the anti-human-CD20 monoclonal antibodies ofatumumab or ocrelizumab alters antibody distribution in humanized CD20 (huCD20) mice, and (2) how administration route affects the efficacy of anti-human-CD20 therapy in a multiple sclerosis (MS) mouse model (huCD20 mice with chronic focal delayed-type hypersensitivity lesions with associated tertiary lymphoid structures (DTH-TLS)).

Induction of focal MS-like lesions in huCD20 mice allows comparison of the efficacies of selective anti-human CD20 therapies in a mouse model. In clinical trials, ofatumumab and ocrelizumab have been shown to be efficacious therapies for relapsing-remitting MS (RRMS). However, ofatumumab is efficacious when given subcutaneously, whereas ocrelizumab is approved for use in RRMS when given intravenously.

Mice expressing human and mouse CD20 on B-cells (huCD20) (n=4 per group) were imaged by single-photon emission computed tomography (SPECT/CT) 72 hours after subcutaneous or intravenous injection of ¹¹¹indium-labeled (¹¹¹In-) ocrelizumab or ¹¹¹In-ofatumumab (5 μg, 5 MBq). The amounts of ¹¹¹In per gram in selected tissues were measured using an automated gamma counter. DTH-TLS lesions were established in huCD20 mice and were treated with ofatumumab and ocrelizumab to compare efficacies.

SPECT/CT imaging revealed a significant increase in ¹¹¹In-ofatumumab and ¹¹¹In-ocrelizumab in axial and inguinal lymph nodes after subcutaneous versus intravenous administration; in fact, accumulation in lymph nodes was greater for subcutaneous ¹¹¹In-ofatumumab than for intravenous ¹¹¹In-ocrelizumab. There was no significant difference in lymph node uptake, as measured by ¹¹¹In per gram, between ¹¹¹In-ocrelizumab and ¹¹¹In-ofatumumab after subcutaneous injection. Ofatumumab and ocrelizumab reduced the size of both the lesion and TLS in the DTH-TLS mouse model.

Subcutaneous administration of ¹¹¹In-ocrelizumab or ¹¹¹In-ofatumumab results in improved lymph node targeting, and accumulation of ¹¹¹In-ofatumumab in lymphoid tissue was greater compared with ¹¹¹In-ocrelizumab.