Biology subjects

Jochimsen, A.

Publications and source records attributed to Jochimsen, A..

2 recordsLinked to original sources

bioRxiv2026

A Novel Natural Killer Cell Expansion Technology for the Development of Cellular Immunotherapies

Adoptive cell therapy based on Natural Killer (NK) cells holds great promise for the treatment of cancer. For all approaches aiming at utilizing NK cells in immunotherapy, efficient ex vivo expansion technologies for the generation on of cytotoxic NK cells are a prerequisite for clinical translation. In this study, a novel multifunctional fusion protein consisting of a CD20-directed Fab-fragment, an agonistic anti-4-1BB single-chain Fragment variable (scFv), the Sushi domain of the interleukin (IL)-15 receptor and human IL-15 was generated. This molecule triggered strong NK cell expansion when bound to co-cultivated autologous B cells, due to trans-presentation of IL-15 and binding to 4-1BB/CD137. Expansion rates of up to 7,500-fold were achieved and the NK cells showed high cytotoxic capacity against a panel of tumor cell lines representing various tumor entities. Importantly, the activated NK cells did not show cytolytic activity against non-malignant B cells indicating that NK cells amplified by our novel approach were still physiologically regulated. The cytotoxic activity of the expanded NK cells was further enhanced by combination with therapeutic antibodies. Our molecule was additionally able to trigger efficient proliferation of NK cells from cord blood as well as multiple myeloma (MM) and acute myeloid leukemia (AML) patients. In conclusion, our novel platform technology provides ex vivo expansion of NK cells by using a single multifunctional fusion protein and may be well-suited for the development of NK cell-based immunotherapies. Key pointsA novel fusion protein that enables NK cell expansion from different sources including peripheral blood, bone marrow and cord blood

immunology↗

bioRxiv2025

CD19xCD3 bispecific T cell engager treatment induces remission in experimental pemphigoid disease

Pemphigoid diseases (PDs) are autoimmune disorders marked by autoantibodies (Aab) against skin and mucous membrane proteins, causing muco-cutaneous blistering in predominantly elderly patients. Since current therapeutics are often insufficient, PDs impose a significant morbidity and mortality burden. CD19xCD3 bispecific T cell engagers (TCEs) - originally developed for B cell malignancies - have shown promise in treatment-refractory autoimmune diseases like systemic sclerosis and rheumatoid arthritis. To explore their potential in PDs, we tested a murine CD19xCD3 TCE in a mouse model of epidermolysis bullosa acquisita (EBA), a prototypical PD. The TCE selectively depleted B cells in blood and bone marrow, but not spleen, of healthy mice. Mice with clinically manifest immunization-induced EBA were randomized to receive either the CD19xCD3 TCE or control treatment upon reaching a predefined disease severity. After 13 weeks, 45% of TCE-treated mice achieved remission, versus 23% of controls. This improvement correlated with reduced antigen-specific B cells, though total and antigen-specific IgG levels were unchanged. These findings suggest that CD19xCD3 TCE preferentially target autoreactive B cells and may be effective at lower doses than those used in oncology. Our data support the potential of CD19xCD3 bispecific T cell engagers as a therapeutic strategy for PDs. eTOC SynopsisGross, Jochimsen, Drager and colleagues demonstrate that CD19xCD3 bispecific T cell engagers, can selectively target autoreactive B cells and induce remission in a mouse model of pemphigoid disease, highlighting their potential as a novel therapeutic strategy for autoimmune blistering disorders.

immunology↗