Despite their potential, bispecific TCRs face several challenges. One of the primary concerns is the risk of cytokine release syndrome (CRS), a potentially severe side effect common to many T-cell engaging therapies. CRS results from the excessive activation of the immune system and can lead to severe inflammation and multi-organ failure. Another challenge is the variability in HLA expression among individuals, which can affect the efficacy of bispecific TCRs. Personalized approaches may be necessary to match the HLA-restricted bispecific TCRs to patients, complicating the treatment process.
