Publications by authors named "N D Brewis"
Unlabelled: Regulatory T cells (Treg) are highly enriched within many tumors and suppress immune responses to cancer. There is intense interest in reprogramming Tregs to contribute to antitumor immunity. OX40 and CD137 are expressed highly on Tregs, activated and memory T cells, and NK cells.
View Article and Find Full Text PDFThe costimulatory receptor CD137 (also known as TNFRSF9 or 4-1BB) sustains effective cytotoxic T-cell responses. Agonistic anti-CD137 cancer immunotherapies are being investigated in clinical trials. Development of the first-generation CD137-agonist monotherapies utomilumab and urelumab was unsuccessful due to low antitumor efficacy mediated by the epitope recognized on CD137 or hepatotoxicity mediated by Fcγ receptors (FcγR) ligand-dependent CD137 activation, respectively.
View Article and Find Full Text PDFTherapeutic antibodies have broad indications across diverse disease states, such as oncology, autoimmune diseases, and infectious diseases. New research continues to identify antibodies with therapeutic potential as well as methods to improve upon endogenous antibodies and to design antibodies de novo. On April 27-30, 2022, experts in antibody research across academia and industry met for the Keystone symposium "Antibodies as Drugs" to present the state-of-the-art in antibody therapeutics, repertoires and deep learning, bispecific antibodies, and engineering.
View Article and Find Full Text PDFArticle Synopsis
- This phase 1 study examined the safety, tolerability, and effectiveness of FS118, a bispecific antibody targeting LAG-3 and PD-L1, in patients with advanced cancer who did not respond to anti-PD-(L)1 therapies.
- A total of 43 patients received FS118 through an intravenous method, demonstrating good tolerance with no serious side effects, and a recommended dosage of 10 mg/kg was established.
- The treatment resulted in a 46.5% disease control rate, primarily through stable disease, highlighting the potential for further research on its clinical benefits in resistant cancer cases.
Purpose: With the increased prevalence in checkpoint therapy resistance, there remains a significant unmet need for additional therapies for patients with relapsing or refractory cancer. We have developed FS222, a bispecific tetravalent antibody targeting CD137 and PD-L1, to induce T-cell activation to eradicate tumors without the current toxicity and efficacy limitations seen in the clinic.
Experimental Design: A bispecific antibody (FS222) was developed by engineering CD137 antigen-binding sites into the Fc region of a PD-L1 IgG1 mAb.