Engineering Heat-resilient Antibodies for Targeted Cancer Hyperthermia

Tumor-targeting hyperthermia (HT) is an emerging therapeutic modality that enhances the efficacy of conventional cancer treatments by generating heat at tumor sites. The combination of antibodies with HT offers a powerful strategy for achieving synergistic therapeutic outcomes with molecularly targeted specificity, thereby minimizing off-target damage to healthy tissues. However, the effectiveness of antibody-based thermal therapies relies on the biophysical stability of antibodies under elevated thermal stress. This necessitates the engineering of antibodies with enhanced thermal stability and overall biophysical properties. This review explores the convergence of antibody engineering and HT applications. First, we summarize the roles of antibodies in various thermal therapy techniques and discuss the critical biophysical properties required for antibody performance in thermal environments. We then discuss engineering strategies to improve thermal robustness, highlighting mammalian cell display as a promising platform that enables phenotypic screening in a biologically relevant folding and quality control environment to enrich for developable, heat-resilient antibody candidates.