Plant Molecular Farming for Cancer Immunotherapy: Production, Glycoengineering, and Structural Insights into Therapeutic Monoclonal Antibodies

Cancer is one of the leading causes of mortality worldwide, creating an urgent need for innovative, scalable, and cost-effective therapeutic strategies. Monoclonal antibodies have transformed modern oncology by enabling highly specific targeting of tumor-associated antigens and immune checkpoint pathways. However, their production in conventional mammalian cell systems remains expensive and requires extensive infrastructure. Plant molecular bioengineering has emerged as a promising alternative platform for the production of recombinant biopharmaceuticals, offering advantages such as rapid scalability, reduced manufacturing costs, biosafety, and flexible expression systems. This review summarizes recent developments in the production of plant-based anticancer biologics, with particular emphasis on therapeutic monoclonal antibodies and immune checkpoint inhibitors. The review includes plant-derived antibodies targeting HER2, PD-1, and PD-L1, which have demonstrated structural integrity, antigen-binding capacity, and biological activity comparable to those of their mammalian-derived counterparts. In this study, we performed a comparative computational structural analysis of trastuzumab and pembrolizumab using experimentally determined antibody structures as references and computationally modeled plant-associated Fc glycoforms, with particular emphasis on Fc N-glycosylation and glycan solvent accessibility. Overall, advances in synthetic biology, precision glycoengineering, and controlled cultivation technologies highlight the potential of plant biofactories as promising platforms for the development of next-generation, affordable, and globally accessible cancer immunotherapies.