Bispecific antibodies and nanotechnology: a strategic alliance in cancer immunotherapy

Bispecific antibodies (bsAbs), designed to recognize two distinct antigens or epitopes, enable innovative mechanisms of action for emerging generations of cancer immunotherapies. Despite their potential, bsAb therapeutics face several challenges related to their biodistribution and pharmacokinetics, which often result in a suboptimal efficacy/toxicity balance. Starting with a brief description of the relevance of bsAbs in cancer immunotherapy, this review aims to critically analyze the synergistic potential of nanotechnology and bsAb technology oriented to enhance therapeutic efficiency while reducing toxicity. This synergy can be achieved through several strategies: (i) bsAbs may function as targeting ligands to improve the biodistribution of drug-loaded nanocarriers; (ii) therapeutic bsAbs incorporated into nanocarriers may easily overcome biological barriers and reach their target; and (iii) bsAbs can be generated in vivo using mRNA-loaded nanocarriers encoding them. This review addresses challenges in these emerging areas and provides insights into future directions for this promising field.