Biopharmaceuticals are medical drugs produced using biotechnology. They include monoclonal antibodies, antibody-drug conjugates, fusion proteins, recombinant cytokines, and gene therapies. Unlike small-molecule drugs, biopharmaceuticals are large, complex macromolecules whose structure determines their therapeutic function, produced in living cells.
Monoclonal antibodies (mAbs) are the largest class of biopharmaceuticals. They are produced by hybridoma technology or recombinant expression systems. Murine antibodies were used initially but elicited immune responses. Chimeric antibodies combine murine variable regions with human constant regions. Humanized antibodies have murine complementarity-determining regions grafted onto human frameworks. Fully human antibodies are generated by phage display or transgenic mice.
mAbs bind to specific antigens with high affinity and mediate therapeutic effects through several mechanisms. Direct antagonism blocks receptor-ligand interactions. Antibody-dependent cell-mediated cytotoxicity recruits immune effector cells. Complement-dependent cytotoxicity activates the complement cascade. Immunomodulation targets immune checkpoints such as PD-1 and CTLA-4.
Antibody-drug conjugates (ADCs) combine the specificity of mAbs with the potency of cytotoxic drugs. The antibody delivers a cytotoxic payload directly to antigen-expressing tumor cells. ADC components include the antibody, a stable linker, and the payload. Linkers are either cleavable (acid-labile, protease-cleavable) or non-cleavable. Payloads include microtubule inhibitors (monomethyl auristatin E, DM1) and DNA-damaging agents (calicheamicin, duocarmycin).
Trastuzumab emtansine (Kadcyla) targets HER2-positive breast cancer with the maytansinoid DM1 payload. Brentuximab vedotin (Adcetris) targets CD30-positive lymphomas with monomethyl auristatin E. Enfortumab vedotin (Padcev) targets Nectin-4 in urothelial carcinoma.
Fusion proteins combine functional domains from different proteins. Etanercept fuses the TNF receptor with an IgG Fc domain to neutralize TNF-α. Abatacept fuses CTLA-4 with Fc to modulate T-cell costimulation. Bispecific antibodies engage two different antigens simultaneously, bridging immune cells to tumor cells or simultaneously blocking two signaling pathways.
Biopharmaceutical development faces challenges including immunogenicity, manufacturing complexity, and high cost. Biosimilars are near-identical versions of approved biopharmaceuticals that provide cost savings after patent expiry.
