ADCC in Skin Disease

Cutaneous Lupus Erythematosus

Lupus erythematosus is a large group of diseases that are chronic, recurrent autoimmune diseases that primarily damage the body's immune system. Cutaneous lupus erythematosus is one of these types. Lesions are mainly confined to the skin. There is a lot of research evidence that antibody-dependent cell-mediated cytotoxicity (ADCC) may be a mechanism for damage to different cellular targets in dermatology.

Fig.1 Schematic diagram of the pathogenic mechanism of cutaneous lupus erythematosus.¹

Advances in the Treatment of Systemic Lupus Erythematosus

At present, the targets for the treatment of systemic lupus erythematosus (SLE) mainly include B cell surface antigens, B cell-related cytokines and their helper molecules, and intracellular small molecule targeted drugs are also very promising. Here, we present only drugs that are relevant to the effects of ADCC.

• Rituximab

Rituximab is a human-mouse chimeric monoclonal antibody that selectively targets CD20 with a human IgG1 domain and a murine CD20 variable region, and has become a standard of care for CD20-expressing B-cell lymphoma and rheumatoid arthritis. The mechanism of rituximab treatment for SLE is inducing apoptosis through ADCC and complement-mediated cytotoxicity, which weakens autoimmune damage to the body through continuous depletion of B cells.

Fig.2 Mechanisms of rituximab and obinutuzumab.²

• Ocrelizumab

Ocrelizumab is an Fc-fragment-modified humanized anti-CD20 monoclonal antibody with higher ADCC activity and lower CDC effect in SLE patients compared to Rituximab, without HACA. However, in several clinical studies of SLE, it was terminated early due to serious adverse events, and the current application of Ocrelizumab in SLE still needs to be verified by a large number of clinical studies.

• Obinutuzumab

Obinutuzumab is the latest generation of fully humanized type II anti-CD20 monoclonal antibody with glyco-modified Fc, which has lower immunogenicity and higher affinity for FcγR III on effector cells than type I anti-CD20 antibody, resulting in stronger ADCCs and better direct B-cell killing. The study confirmed that Obinutuzumab was at least 2 times more efficient at inducing B cell toxicity in rheumatoid arthritis and SLE in vitro whole blood assays than Rituximab.

You can find more information about Obinutuzumab by clicking here!

• NK/CAR-T cell therapy

Recently, a non-GMO, cord blood-derived allogeneic, cryopreserved NK cell therapy candidate has been used to treat SLE and is designed to enhance ADCC effects. This drug has been used in combination with allogeneic NK therapy with Rituximab for the treatment of SLE in patients with active lupus nephritis (LN).

Creative Biolabs has been committed to enhancing the development of ADCC in different fields, relying on a strong R&D team and advanced technology platform, we have been in the leading position in the field of ADCC!

References

1. Niebel, D.; et al. "Cutaneous lupus erythematosus: an update on pathogenesis and future therapeutic directions." American Journal of Clinical Dermatology. (2023): 521-540.
2. Freeman.; et al. "A tale of two antibodies: obinutuzumab versus rituximab." British Journal of Haematology. (2018): 29-45.