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Therapeutic monoclonal antibodies
E H Choy1, G S Panayi, G H Kingsley
1Rheumatology Unit, UMDS, Guy's Hospital, London.
British Journal of Rheumatology
|August 1, 1995
Summary
Monoclonal antibodies targeting tumor necrosis factor alpha show clinical efficacy in rheumatoid arthritis (RA) but offer limited duration. Lymphocyte depletion strategies are disappointing, but non-depleting antibodies and combination therapies show promise for long-term RA remission.
Area of Science:
- Immunology
- Rheumatology
- Biotechnology
Background:
- Monoclonal antibodies are increasingly utilized in rheumatoid arthritis (RA) clinical trials.
- They serve as both therapeutic agents and tools to study RA immunopathogenesis.
- Anti-tumor necrosis factor alpha (TNF alpha) antibodies demonstrate clinical effectiveness in RA.
Purpose of the Study:
- To evaluate the efficacy and limitations of monoclonal antibodies in rheumatoid arthritis treatment.
- To explore alternative antibody-based strategies for achieving long-term disease remission in RA.
Main Methods:
- Clinical trials involving anti-TNF alpha monoclonal antibodies.
- Assessment of lymphocyte-depleting antibodies in RA models.
- Investigation of non-depleting anti-CD4 antibodies and combination antibody therapies (anti-CD4 and anti-TNF alpha) in animal models of RA.
Main Results:
- Anti-TNF alpha antibodies provide rapid but short-lived (4-6 weeks) clinical improvement in RA.
- Re-treatment with anti-TNF alpha antibodies remains effective, but long-term data is needed.
- Lymphocyte-depleting antibodies have shown disappointing results due to difficulties in eliminating synovial lymphocytes and risks of severe immunosuppression.
- Non-depleting anti-CD4 antibodies have induced long-term remission in animal models of RA.
- Combination therapy with anti-CD4 and anti-TNF alpha antibodies demonstrated synergistic effects in murine collagen-induced arthritis.
Conclusions:
- While anti-TNF alpha antibodies are effective for short-term RA symptom relief, their long-term role requires further study.
- Lymphocyte depletion is likely not a viable therapeutic strategy for RA due to safety concerns.
- Non-depleting antibodies targeting CD4 lymphocytes and combination antibody therapies represent promising avenues for achieving sustained remission in RA.