Table 2 Clinical studies of immune checkpoint-based immunotherapies in MS patients
From: Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice
Study design | Subjects | Target ICP | Intervention | Outcome | Reference |
|---|---|---|---|---|---|
Phase 1, open-label, clinical trial | 16 RRMS | CTLA-4 | RG2077 (recombinant CTLA4-IgG4m) | The treatment reduced MBP proliferation and IFN-γ secretion by MBP-specific cells with only mild side effects. | [170] |
Phase II, randomized, clinical trial | 65 RRMS | CTLA-4 | Abatacept (CTLA-4 Ig fusion protein) or Placebo | No substantial differences were observed between the Abatacept and placebo groups in terms of the mean number of new Gd+ MRI lesions or other MRI and clinical parameters of disease activity. | [171] |
Phase II, randomized, clinical trial | 65 RRMS | CTLA-4 | Abatacept (CTLA-4 Ig fusion protein) or Placebo | Abatacept treatment drastically lowered the relative frequencies of Treg and Tfh cells in circulating CD4+ T cells, as well as circulating plasmablasts. compared to a placebo. It suppressed their activity by downregulating activation markers, such as CD38 and ICOS genes, which are implicated in cell division and chromatin dynamics in these cells. | [172] |
Case report | 1 MS | CTLA-4 | Abatacept (CTLA-4 Ig fusion protein) | After a two-year period, significant improvements were noted in MRI findings, demonstrating the absence of any definitive abnormal enhancing lesion in the brain parenchyma. These positive changes were accompanied by improvements in clinical symptoms. | [173] |
Phase 1, open-label, clinical trial | 12 RRMS | CD40L | Toralizumab/IDEC-131 (Humanized αCD40L) | The treatment resulted in an enhancement of the CD25+/CD3+ and CD25+/CD4+ ratios and a shift towards an anti-inflammatory cytokine response.The treatment resulted in an enhancement of the CD25+/CD3+ and CD25+/CD4+ ratios and a shift towards an anti-inflammatory cytokine response. | [174] |