{"id":2027,"date":"2026-05-17T09:01:00","date_gmt":"2026-05-17T09:01:00","guid":{"rendered":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/05\/17\/were-we-ahead-of-our-time-with-alemtuzumab\/"},"modified":"2026-05-17T09:01:00","modified_gmt":"2026-05-17T09:01:00","slug":"were-we-ahead-of-our-time-with-alemtuzumab","status":"publish","type":"post","link":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/05\/17\/were-we-ahead-of-our-time-with-alemtuzumab\/","title":{"rendered":"Were we ahead of our time with Alemtuzumab?"},"content":{"rendered":"
Tweet<\/a><\/div>\n

Many years ago I was chastized by a number of people notably from Pharma for suggesting that immue tolerance was lost following alemtuzumab leading to secondary autoimmunities and anti-drug antibodies and this was consistent with the loss of T regulatory cells, but my ideas were rubbished. <\/p>\n

It lost us a grant.<\/p>\n

It was said that T regulatory cells increased. As a percentage compared to other CD4 T cells maybe yes, but when you look at the absolute number of T regulatory cells they dramatically decreased.<\/p>\n

If they went up why would the folks at Cambridge want to increase the number of T regs in this stduy. They tried to do this here using a T cell growth factor interleukin 2 and concluded it wasn’t the way foward.<\/p>\n

Abstract.<\/p>\n

Regulatory T cells (Tregs) are essential for preventing autoimmunity. They depend upon interleukin-2 (IL-2) for optimal function and due to high expression of the CD25 subunit of the IL-2 receptor, are 10-fold more sensitive to IL-2 than effector T cells (Teffs). Consequently low-dose IL-2 can be used to preferentially expand Tregs, a therapeutic strategy which has shown promise in a number of autoimmune and inflammatory conditions – including graft-versus-host disease and lupus, where IL-2 driven expansion correlates with improvements in some clinical markers of disease activity. Autoimmunity is a frequent delayed complication of treatment with the lymphocyte-depleting drug alemtuzumab in relapsing-remitting multiple sclerosis (RRMS). Here, using in vitro assays, a pre-clinical mouse model, and an experimental medicine study, we investigated whether low-dose IL-2 could selectively expand Tregs in alemtuzumab-treated RRMS patients. Six months after alemtuzumab treatment, the frequency of patient-derived na\u00efve CD4+ Teffs expressing high-affinity IL-2 receptors increased from 30.11+\/-5.09% to 72.88 +\/-5.57%, and the density of receptors per cell increased, rendering them six times more sensitive to IL-2 in vitro, at concentrations that typically favour Tregs. Using a human CD52-expressing transgenic mouse model of alemtuzumab treatment, we found that IL-2 was still able to preferentially expand Tregs, but only when administered at a later time point, corresponding to more than 6 months post-treatment in patients. Guided by these findings, we evaluated low-dose IL-2 for Treg expansion in a prospective open-label mechanistic study of RRMS patients who had received alemtuzumab more than 6 months previously. IL-2, at a dose and frequency similar to that previously shown to expand Tregs in autoimmune diabetes (0.3 x 106 IU\/m2 twice a week), was well tolerated and safe, but unexpectedly failed to expand Tregs. We discuss the potential reasons underlying this lack of response, ruling out sIL2RA-related neutralisation, and instead considering ceiling effects on Treg proliferation, Treg exhaustion and intrinsic Treg dysfunction in MS as possible contributors. Together, our findings demonstrate that low-dose IL-2 alone is not an effective strategy for promoting Treg expansion post-alemtuzumab, and is therefore not a viable approach by itself for preventing post-treatment autoimmune complications.<\/p>\n

Interleukin 2 is a T cell growth factor as well as molecule that can augment Tregulatory cells. It is also a growth factor for memory B cells…Do we want to make more of these cells…..<\/p>\n<\/p>\n

Source: multiple-sclerosis-research.org<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Tweet Many years ago I was chastized by a number of people notably from Pharma for suggesting that immue tolerance was lost following alemtuzumab leading to secondary autoimmunities and anti-drug antibodies and this was consistent with the loss of T regulatory cells, but my ideas…<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[11,15,9,8,13,14,12,10],"class_list":["post-2027","post","type-post","status-publish","format-standard","hentry","category-multiple-sclerosis-research","tag-brain-repair","tag-marburg-type-ms","tag-ms","tag-multiple-sclerosis","tag-myelin","tag-neuroregeneration","tag-oligodendrocyte","tag-remyelination"],"_links":{"self":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/2027","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/comments?post=2027"}],"version-history":[{"count":0,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/2027\/revisions"}],"wp:attachment":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/media?parent=2027"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/categories?post=2027"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/tags?post=2027"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}