maybe B-cells are not so important

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frodo
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maybe B-cells are not so important

Post by frodo » Sun Feb 03, 2019 7:41 am

The success of anti-CD20 monoclonal antibodies has put the focus on CD20 B-cells, but it could be that the mechanism of action is about depleting CD20+ T-cells.

Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients

https://www.mdpi.com/2073-4409/8/1/12

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3+CD20+ T cells) also expresses CD20, and these CD20+ T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3+ T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45+ lymphocytes, and constituted a significant proportion (18.4%) of all CD20+ cells. CD3+CD20+ T cells and CD19+CD20+ B cells were effectively depleted two weeks after a single administration of 300 mg ocrelizumab. Our results demonstrate that treatment with ocrelizumab does not exclusively target B cells, but also CD20+ T cells, which account for a substantial amount of CD20-expressing cells. Thus, we speculate that the efficacy of ocrelizumab might also be mediated by the depletion of CD20-expressing T cells. View Full-Text

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Re: maybe B-cells are not so important

Post by NHE » Sun Feb 03, 2019 8:07 am

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS).
The following graph is from Ocrevus' prescribing information. The differences in disability progression between Ocrevus and placebo certainly don't appear to be very pronounced. Am I missing something?


Image

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Re: maybe B-cells are not so important

Post by frodo » Sun Feb 03, 2019 9:43 am

I would say that for "reduction of disease activity" they mean relapses, not progresion.

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