Publications by authors named "Sarah Diggelmann"

Article Synopsis
  • Multiple myeloma (MM) is still an incurable cancer despite available therapies, with T-cell bispecific antibodies (TCBs) targeting BCMA and GPRC5D showing promise but facing issues like resistance and relapse due to antigen loss.
  • Forimtamig is a novel GPRC5D-targeting TCB that works more effectively than traditional formats by forming stable immunological connections, leading to better tumor cell destruction and T cell activation in preclinical studies.
  • Current research is exploring forimtamig in clinical trials for relapsed and refractory MM patients, both alone and alongside traditional care and new therapies, to enhance treatment outcomes and prevent relapses.
View Article and Find Full Text PDF

Targeted T-cell redirection is a promising field in cancer immunotherapy. T-cell bispecific antibodies (TCB) are novel antibody constructs capable of binding simultaneously to T cells and tumor cells, allowing cross-linking and the formation of immunologic synapses. This in turn results in T-cell activation, expansion, and tumor killing.

View Article and Find Full Text PDF

Endogenous costimulatory molecules on T cells such as 4-1BB (CD137) can be leveraged for cancer immunotherapy. Systemic administration of agonistic anti-4-1BB antibodies, although effective preclinically, has not advanced to phase 3 trials because they have been hampered by both dependency on Fcγ receptor-mediated hyperclustering and hepatotoxicity. To overcome these issues, we engineered proteins simultaneously targeting 4-1BB and a tumor stroma or tumor antigen: FAP-4-1BBL (RG7826) and CD19-4-1BBL.

View Article and Find Full Text PDF

Despite promising clinical activity, T-cell-engaging therapies including T-cell bispecific antibodies (TCB) are associated with severe side effects requiring the use of step-up-dosing (SUD) regimens to mitigate safety. Here, we present a next-generation CD20-targeting TCB (CD20-TCB) with significantly higher potency and a novel approach enabling safer administration of such potent drug. We developed CD20-TCB based on the 2:1 TCB molecular format and characterized its activity preclinically.

View Article and Find Full Text PDF

Cadazolid (CDZ) is a new antibiotic currently in clinical development for the treatment of infections. CDZ interferes with the bacterial protein synthesis machinery. The aim of the present study was to identify resistance mechanisms for CDZ and compare the results to those obtained for linezolid (LZD) in by whole-genome sequencing (WGS) of strains generated by passages and to those obtained for LZD-resistant clinical isolates.

View Article and Find Full Text PDF