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Summary: This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan‐Hu‐1 RBD of SARS‐CoV‐2. We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human‐like, highly homogenous N‐linked glycans that has potential to impart greater potency and safety as a therapeutic. The epitope of 11D7 was mapped by competitive binding with well‐characterized mAbs, suggesting that it is a Class 4 RBD‐binding mAb that binds to the RBD outside the ACE2 binding site. Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. Taken together, 11D7 is a unique mAb that neutralizes SARS‐CoV‐2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety‐friendly alternative platform for generating mAbs to address the evolving SARS‐CoV‐2 crisis. [ABSTRACT FROM AUTHOR]

Men with high-risk localized prostate cancer exhibit high rates of post-surgical recurrence. In these patients, androgen deprivation therapy (ADT) is immunomodulatory, however increased infiltration of regulatory T cells (Tregs) may limit the antitumor immune effects of ADT. We designed a neoadjuvant clinical trial to test whether BMS-986218 - a next-generation non-fucosylated anti-CTLA-4 antibody engineered for enhanced antibody-dependent cellular cytotoxicity or phagocytosis (ADCC/P) - depletes intratumoral Tregs and augments the response to ADT. In this single-center, two-arm, open-label study, 24 men with high-risk localized prostate cancer were randomized to receive a single dose of ADT with or without two pre-operative doses of BMS-986218 (anti-CTLA4-NF) prior to radical prostatectomy. Treatment was well tolerated and feasible in the neoadjuvant setting. A secondary clinical outcome was the rate of disease recurrence, which was lower than predicted in both arms. Mechanistically, anti-CTLA4-NF reduced ADT-induced Treg accumulation through engagement of CD16a/ FCGR3A on tumor macrophages, and depth of Treg depletion was quantitatively associated with clinical outcome. Increased intratumoral dendritic cell (DC) frequencies also associated with lack of recurrence, and pre-clinical data suggest ADCC/P-competent anti-CTLA-4 antibodies elicit activation and expansion of tumor DCs. Patients receiving anti-CTLA4-NF also exhibited phenotypic signatures of enhanced antitumor T cell priming. In total, this study provides the first-in-human evidence of Treg depletion by glycoengineered antibodies targeting CTLA-4 in humans and their potential in combination with ADT in prostate cancer patients with high-risk of recurrence., Competing Interests: Conflicts of Interest: C.G.D is a co-inventor on patents licensed from Johns Hopkins University to BMS and Janssen. He is currently a paid employee of JnJ Innovative Medicine. A.C. is founder, equity holder, consultant, and director of DarwinHealth Inc., which has licensed IP related to these algorithms from Columbia University. Columbia University is an equity holder in DarwinHealth Inc.

Recombinant proteins have a broad range of applications from basic research to pharmaceutical development. Of utmost importance in the production of recombinant proteins is the selection of the best recombinant protein production system, such that high-quality and functional recombinant proteins are produced. Plants can produce a large quantity of recombinant proteins rapidly and economically. Glycoengineering has created "humanized" plant lines that can produce glycoproteins with specific human glycans with a high level of homogeneity on demand. Here, a detailed protocol was provided to produce a large, multisubunit, and complex bispecific antibody that targets two distinct viruses. The successful production of this multiple-subunit protein demonstrated that plants are the optimal system for the production of recombinant proteins of various sizes and complexity, which can be employed for various applications including diagnostics, therapeutics, and vaccines to combat current and future pandemics., (Copyright © 2021 Elsevier Inc. All rights reserved.)