Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4.
We have previously shown that anti-tumour necrosis factor (TNF) monoclonal antibody (mAb) ameliorates established collagen-induced arthritis and that the efficacy of this form of treatment can be enhanced by concurrent anti-CD4 treatment. Here we assess the efficacy of a human p55 TNF receptor-IgG f...
| Glavni autori: | , , , |
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| Format: | Journal article |
| Jezik: | English |
| Izdano: |
1995
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| _version_ | 1826278563840524288 |
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| author | Williams, R Ghrayeb, J Feldmann, M Maini, R |
| author_facet | Williams, R Ghrayeb, J Feldmann, M Maini, R |
| author_sort | Williams, R |
| collection | OXFORD |
| description | We have previously shown that anti-tumour necrosis factor (TNF) monoclonal antibody (mAb) ameliorates established collagen-induced arthritis and that the efficacy of this form of treatment can be enhanced by concurrent anti-CD4 treatment. Here we assess the efficacy of a human p55 TNF receptor-IgG fusion protein (p55-sf2), given alone or with anti-CD4 mAb. TNF receptor-IgG fusion protein (100 micrograms) suppressed paw swelling and limb recruitment in established arthritis and reduced the incidence of erosions in the proximal interphalangeal joints from 92% to 50%, which was comparable to 41% erosions using anti-TNF mAb. Methylprednisolone acetate (4.2 mg/kg/week) reduced clinical signs of inflammation in a manner comparable to TNF blockade but had little effect on the incidence of erosions. Co-administration of anti-CD4 and TNF receptor-IgG led to an even greater therapeutic effect than TNF receptor-IgG alone, with the incidence of erosions being reduced from 100% to 17%. Serological analyses showed that the beneficial effects of anti-CD4 and TNF receptor-IgG could be partly explained by the ability of anti-CD4 to prevent a neutralizing antibody response. These results confirm the importance of TNF in destructive inflammatory arthritis and demonstrate the feasibility of therapeutically targeting TNF with a form of TNF receptor. Finally, the findings confirm the beneficial effects of TNF-targeted therapy coupled with anti-CD4 therapy. |
| first_indexed | 2024-03-06T23:45:48Z |
| format | Journal article |
| id | oxford-uuid:70d6d721-d26c-456f-b19d-c0b07d20c721 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:45:48Z |
| publishDate | 1995 |
| record_format | dspace |
| spelling | oxford-uuid:70d6d721-d26c-456f-b19d-c0b07d20c7212022-03-26T19:39:55ZSuccessful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:70d6d721-d26c-456f-b19d-c0b07d20c721EnglishSymplectic Elements at Oxford1995Williams, RGhrayeb, JFeldmann, MMaini, RWe have previously shown that anti-tumour necrosis factor (TNF) monoclonal antibody (mAb) ameliorates established collagen-induced arthritis and that the efficacy of this form of treatment can be enhanced by concurrent anti-CD4 treatment. Here we assess the efficacy of a human p55 TNF receptor-IgG fusion protein (p55-sf2), given alone or with anti-CD4 mAb. TNF receptor-IgG fusion protein (100 micrograms) suppressed paw swelling and limb recruitment in established arthritis and reduced the incidence of erosions in the proximal interphalangeal joints from 92% to 50%, which was comparable to 41% erosions using anti-TNF mAb. Methylprednisolone acetate (4.2 mg/kg/week) reduced clinical signs of inflammation in a manner comparable to TNF blockade but had little effect on the incidence of erosions. Co-administration of anti-CD4 and TNF receptor-IgG led to an even greater therapeutic effect than TNF receptor-IgG alone, with the incidence of erosions being reduced from 100% to 17%. Serological analyses showed that the beneficial effects of anti-CD4 and TNF receptor-IgG could be partly explained by the ability of anti-CD4 to prevent a neutralizing antibody response. These results confirm the importance of TNF in destructive inflammatory arthritis and demonstrate the feasibility of therapeutically targeting TNF with a form of TNF receptor. Finally, the findings confirm the beneficial effects of TNF-targeted therapy coupled with anti-CD4 therapy. |
| spellingShingle | Williams, R Ghrayeb, J Feldmann, M Maini, R Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. |
| title | Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. |
| title_full | Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. |
| title_fullStr | Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. |
| title_full_unstemmed | Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. |
| title_short | Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. |
| title_sort | successful therapy of collagen induced arthritis with tnf receptor igg fusion protein and combination with anti cd4 |
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