Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment

Abstract

Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target binding affinity, serum half-life, stability, and immunogenicity. In this review, we highlight some of these strategies and provide examples of modified and engineered proteins under development as preclinical and clinicalstage drug candidates for treating cancer.

Cyclotides: Overview and Biotechnological Applications

“…[2] Protein and peptide-based therapeutics have several advantages when targeting protein-protein interactions due to their high specificity and selectivity. [3] However, they also show important limitations such as limited stability to proteolysis and inability to cross biological membranes. [4] In response to this challenge, a number of technologies are starting to emerge to address these issues.…”

“…[4] In response to this challenge, a number of technologies are starting to emerge to address these issues. [3d, 5] …”

Technologies and Strategies for Bioanalysis of Biopharmaceuticals

“…It is important to understand during assay development what forms of the biotherapeutics are most relevant to pharmacological assessment, which technology to use to measure the intended forms or variants, and to incorporate sound assay reagent gen-future science group Foreword Zhang & An eration and characterization strategies. Furthermore, protein biologics almost exclusively target extracellular proteins due to limitations in intracellular delivery of large biomacromolecules [5]. This leaves many promising untapped intracellular targets, propelling significant efforts to develop proteins capable of accessing and binding targets inside the cell.…”

“…In particular, mAbs constitute the fastest growing sector within the therapeutic protein industry, resulting in occupying about half of the biopharmaceutical market [3]. The success of mAbs in the pharmaceutical market has triggered the development of various antibody-based therapeutics such as multispecific mAbs, antibody-drug conjugates, and Fc fusion proteins with an aim of increasing target -binding affinity and selectivity, extending half-life, and reducing immunogenicity and toxicity [1,[4][5]. In addition, the field has turned to so-called 'alternative protein scaffolds', which are smaller and more modular than their antibody counterparts, to address the limitation of antibodies [5].…”

“…The success of mAbs in the pharmaceutical market has triggered the development of various antibody-based therapeutics such as multispecific mAbs, antibody-drug conjugates, and Fc fusion proteins with an aim of increasing target -binding affinity and selectivity, extending half-life, and reducing immunogenicity and toxicity [1,[4][5]. In addition, the field has turned to so-called 'alternative protein scaffolds', which are smaller and more modular than their antibody counterparts, to address the limitation of antibodies [5]. In parallel, the patents related top-selling biopharmaceuticals have reached their expiration and more will expire within the next few years [6], resulting in explosive creation of opportunities for biosimilar manufacturers to market their own generic versions of biopharmaceuticals [7,8].…”