Relevance of anti-myelin antibodies in Multiple Sclerosis

Antibodies directed against myelin antigens have been described in multiple sclerosis (MS). Although anti-myelin antibodies have been implicated in central nervous system (CNS) demyelination, it is unclear to what extent anti-myelin antibodies contribute to MS pathogenesis. In this dissertation, the role of antibodies in MS and in the animal model experimental allergic encephalomyelitis (EAE) is addressed in eight chapters: Chapter 1: A review on antibodies, complement and Fc receptors in MS Chapter 2: A review on antibodies, complement and Fc receptors in several models of EAE Chapter 3: An in vivo study to the role Fcgamma receptors (FcgR), and interactions between FcgR and anti-MOG antibodies in EAE Chapter 4: A genetic study on FcgR polymorphisms in MS patients and healthy donors Chapter 5: An immunohistochemical study to describe deposition of complement activation products, antibodies and expression of FcgR in active demyelinating MS lesions Chapter 6: The description of a new method to measure antibodies to human whole myelin in human serum Chapter 7: Application of the myelin flow cytometry assay to study the clinical relevance of anti-myelin antibodies Chapter 8: Summary and discussion of the previous chaptersDijkstra, C.D. [Promotor]Amor, S. [Copromotor]Bö, L. [Copromotor

Cerebrospinal fluid anti-myelin antibodies are related to magnetic resonance measures of disease activity in multiple sclerosis

0.001), together constituting 85% of all positive CSF samples. In contrast, elevated anti-myelin IgG antibody reactivity was present in a minority of IND patients (21%), marginally present in controls (5%) and absent in OND patients (0%). Most strikingly, anti-myelin IgG antibody reactivity was related to the number of T2 lesions (r = 0.31, p = 0.041) and gadolinium enhancing T1 lesions (r = 0.37, p = 0.016) on brain MRI in CIS and relapse onset MS patients. Conclusion: CSF anti-myelin IgG antibodies are promising specific biomarkers in CIS and relapse onset MS and correlate with MR measures of disease activit

Potent preclinical efficacy of DuoHexaBody-CD37 in B-cell malignancies

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Response to Comment on "Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells"

Transplantation and autoimmunit

Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer

Targeted therapies and immunotherapy have shown promise in patients with non-small cell lung cancer (NSCLC). However, the majority of patients fail or become resistant to treatment, emphasizing the need for novel treatments. In this study, we confirm the prognostic value of levels of AXL, a member of the TAM receptor tyrosine kinase family, in NSCLC and demonstrate potent antitumor activity of the AXL-targeting antibody-drug conjugate enapotamab vedotin across different NSCLC subtypes in a mouse clinical trial of human NSCLC. Tumor regression or stasis was observed in 17/61 (28%) of the patient-derived xenograft (PDX) models and was associated with AXL mRNA expression levels. Significant single-agent activity of enapotamab vedotin was validated in vivo in 9 of 10 AXL-expressing NSCLC xenograft models. In a panel of EGFR-mutant NSCLC cell lines rendered resistant to EGFR inhibitors in vitro, we observed de novo or increased AXL protein expression concomitant with enapotamab vedotin-mediated cytotoxicity. Enapotamab vedotin also showed antitumor activity in vivo in 3 EGFR-mutant, EGFR inhibitor-resistant PDX models, including an osirnertinib-resistant NSCLC PDX model. In summary, enapotamab vedotin has promising therapeutic potential in NSCLC. The safety and preliminary efficacy of enapotamab vedotin are currently being evaluated in the clinic across multiple solid tumor types, including NSCLC.Transplantation and autoimmunit

Duohexabody-CD37, a Novel Bispecific Antibody with a Hexamerization-Enhancing Mutation Targeting CD37, Demonstrates Superior Complement-Dependent Cytotoxicity in Preclinical B-Cell Malignancy Models

Transplantation and autoimmunit

Duobody-CD3xCD20 Shows Unique and Potent Preclinical Anti-Tumor Activity in Vitro and In Vivo, and Is Being Evaluated Clinically in Patients with B-Cell Malignancies

Transplantation and autoimmunit