Repurposing of rituximab biosimilars to treat B cell mediated autoimmune diseases

Mostkowska, Agata; Rousseau, Guy; Raynal, Noël J-M

doi:10.1101/2023.09.22.23295633

Cited by 2 publications

(2 citation statements)

References 215 publications

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“…Notably, patients with anti-CV2/CRMP5 autoimmunity are often diagnosed with cancer. Treatment with anti-CD20 bears the potential to synergize with classical chemotherapeutics (33) which could help with the elimination of primary tumors additionally to relieving autoimmune pain. Furthermore, pain is a significant comorbidity in cancer patients, and addressing pain in anti-CV2/CRMP5 patients can profoundly impact their quality of life and survival post-cancer diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…( 32)) for its potential as a long-term therapy to reverse pain from CRMP5 autoimmune painful neuropathy. Anti-CD20 specifically targets B lymphocytes as autoantibody producing cells (33) and is currently used to treat conditions such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, and refractory rheumatoid arthritis. We administered anti-CD20 on day 56 and then day 63 to rats with CRMP5 autoimmunity.…”

Section: Preclinical Evaluation Of Potential Therapies For Crmp5 Auto...mentioning

confidence: 99%

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Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain

Martin,

Stratton,

Gomez

et al. 2024

Preprint

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Paraneoplastic neurological syndromes arise from autoimmune reactions against nervous system antigens due to a maladaptive immune response to a peripheral cancer. Patients with small cell lung carcinoma or malignant thymoma can develop an autoimmune response against the CV2/collapsin response mediator protein 5 (CRMP5) antigen. For reasons that are not understood, approximately 80% of patients experience painful neuropathies. Here, we investigated the mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related pain. We found that patient-derived CV2/CRMP5-Abs can bind to their target in rodent dorsal root ganglia (DRG) and superficial laminae of the spinal cord. CV2/CRMP5-Abs induced DRG neuron hyperexcitability and mechanical hypersensitivity in rats that were abolished by preventing binding to their cognate autoantigen CRMP5. The effect of CV2/CRMP5-Abs on sensory neuron hyperexcitability and mechanical hypersensitivity observed in patients was recapitulated in rats using genetic immunization providing an approach to rapidly identify possible therapeutic choices for treating autoantibody-induced pain including the repurposing of a monoclonal anti-CD20 antibody that selectively deplete B-lymphocytes. These data reveal a previously unknown neuronal mechanism of neuropathic pain in patients with paraneoplastic neurological syndromes resulting directly from CV2/CRMP5-Abs-induced nociceptor excitability. CV2/CRMP5-Abs directly sensitize pain responses by increasing sensory neuron excitability and strategies aiming at either blocking or reducing CV2/CRMP5-Abs can treat pain as a comorbidity in patients with paraneoplastic neurological syndromes.

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Section: Discussionmentioning

confidence: 99%

Section: Preclinical Evaluation Of Potential Therapies For Crmp5 Auto...mentioning

confidence: 99%

Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain

Martin,

Stratton,

Gomez

et al. 2024

Preprint

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Pharmacotherapy of autoimmune rheumatic diseases – from monoclonal antibodies to CAR T cells: 20 years later

Nasonov,

Rumyantsev,

Samsonov

2024

Naučno-praktičeskaâ revmatologiâ

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Autoimmunity is a pathological process associated with a violation of immunological tolerance to normal structural components of the body (autoantigens), associated with the predominance of active (adaptive) immunity and manifested by hyperproduction of autoantibodies. Systemic autoimmune rheumatic diseases (SARDs) are among the most common and severe nosological forms of this pathology associated with autoimmunity. Problems of pharmacotherapy of SARDs are the subject of intensive research. At the beginning of the 21st century, more than 20 biologic agents were developed for the treatment of rheumatoid arthritis – monoclonal antibodies (mAbs) and recombinant proteins that control inflammation associated with the overproduction of “pro-inflammatory” cytokines, the use of which has dramatically improved the results of pharmacotherapy. However, much less research has been devoted to studying the possibilities of pharmacotherapy aimed at selective suppression of the “autoimmune” component of the pathogenesis of SADRs associated with uncontrolled activation of B cells and restoration of immunological tolerance to autoantigens. In the spectrum of drugs whose mechanism of action is associated with the suppression of pathological activation of B cells, the leading place is occupied by rituximab (RTM). It is noteworthy that 20 years ago (2004), a group of researchers led by prof. J.C. Edwards first demonstrated the effectiveness of RTM in patients with RA, which was soon successfully repositioned to treat a wide range of SARDs. A major achievement in the pharmacotherapy of SARDs is associated with the use of CAR (сhimeric antigen receptor) T cell therapy, developed for the treatment of refractory hematological tumors. The main component of CART-cells is a genetically engineered T-cell receptor that recognizes the target antigen without the participation of the major histocompatibility complex. Although limited, extremely impressive data regarding high remission rates have been obtained by adapting CD19 CART-cell therapy to treat patients with severe systemic lupus erythematosus (SLE) and other SARDs refractory to standard immunosuppressive medications. The article discusses the results of the use of CART-cell therapy in SLE and other SARDs and prospects for further research.

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Repurposing of rituximab biosimilars to treat B cell mediated autoimmune diseases

Cited by 2 publications

References 215 publications

Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain

Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain

Pharmacotherapy of autoimmune rheumatic diseases – from monoclonal antibodies to CAR T cells: 20 years later

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