ABSTRACT
Purpose: After nearly 3 years of the COVID-19 pandemic, even though a vast body of knowledge and products (including vaccines and treatments) have been developed and disseminated, the virus is still evolving and new variants arising. Consequently, thousands of lives continue to be lost. Neutralizing monoclonal antibodies (nAbs) are promising drugs that emerged to treat SARS-CoV-2. In the uncertainty of the current situation, there is the question of whether organizations should continue to invest in this technology. To help decision-making in scientifical and pharmaceutical organizations, it is of major importance to monitor the development of products and technologies. Therefore, the aim of this study is analyze the landscape of nAbs for COVID-19. Methods: The scenario of 473 biotherapeutics focusing on nAbs was evaluated using foresight techniques and a review of literature. Data were obtained from structured and semi-structured databases and processed for treatment, cleaning, consistency, validation, and enrichment. Results: We identified 227 nAbs and performed an extensive literature review of 16 nAbs in late clinical development, including development technologies, responses to variants of concern (VOCs), manufacturing, and clinical aspects. Conclusions: Even though the emergence of new VOCs is a threat to the effectiveness of this treatment, demanding constant genomic surveillance, the use of nAbs to treat and prevent COVID-19 will probably continue to be relevant due to excellent safety profiles and the possibility of immediate immunity transfer, especially in patients showing inadequate immunological response to vaccination. Therefore, we suggest that organizations should keep investing in improvements in this technology.
ABSTRACT
Antibodies that block interaction of immune checkpoint receptors with its ligands have revolutionized the treatment of several cancers. Despite the success of this approach, the high cost has been restricted the use of this class of drugs. In this context, the development of biosimilar can be an important strategy for reducing prices and expanding access after patent has been dropped. Here, we evaluated the use of HEK293 cells for transient expression of an immune checkpoint-blocking antibody as a first step for biosimilar development. Antibody light and heavy chain genes were cloned into pCI-neo vector and transiently expressed in HEK293 cells. The culture supernatant was then subjected to protein A affinity chromatography, which allowed to obtain the antibody with high homogeneity. For physicochemical comparability, biosimilar antibody and reference drug were analyzed by SDS-PAGE, isoelectric focusing, circular dichroism and fluorescence spectroscopy. The results indicated that the both antibodies have a high degree of structural similarity. Lastly, the biosimilar antibody binding capacity to target receptor was shown to be similar to reference product in ELISA and flow cytometry assays. These data demonstrate that the HEK293 system can be used as an important tool for candidate selection and early development of biosimilar antibodies.
