Bispecific Antibodies Advance in Hematologic Cancers as Structural Stability Concerns Emerge
Presenters at the 2026 ICE-T Conference discussed the growing role of bispecific antibodies and CAR T-cell therapies in hematologic cancers, while a separate study found that structural instability of linkers in symmetric bispecific antibodies could pose manufacturing hurdles.
Bispecific antibodies are reshaping treatment approaches for multiple myeloma and lymphoma, according to experts at the 2026 National ICE-T Conference in Orlando, while a separate laboratory study highlights potential manufacturing challenges related to linker stability. One presentation at the conference noted that bispecific T-cell engagers are altering the landscape of multiple myeloma care and will eventually become an option in the frontline setting. With many products to choose from, the presenter emphasized sequencing these novel therapies wisely and stressed aggressive infection prophylaxis as a mandatory facet of care. In relapsed/refractory follicular lymphoma, a debate covered the roles of bispecific antibodies and CAR T-cell therapies. One hematologist-oncologist argued that bispecific antibodies should be used prior to CAR T-cell therapy for most patients, although both treatments have utility. Another specialist advocated for CAR T-cell therapy but acknowledged that both modalities can make up a complementary strategy. Challenges with CAR T-cell toxicity were discussed, including the difficulty of differentiating immune effector cell-associated HLH-like syndrome (IEC-HS) from cytokine release syndrome (CRS), and the lack of a definitive threshold for initiating prophylaxis. Meanwhile, a separate study examined the structural stability of a symmetric bispecific antibody targeting HER2 and CD3. The molecule exhibited pronounced fragmentation under prolonged thermal stress, particularly when combined with high pH and salt conditions. Intact mass analysis identified sequential clipping along G4S and G4 linkers, as well as fragmentation at interchain cystinyl residues and cleavage at the C-terminal of asparagine residues. The identification of G4S and G4 linkers as vulnerable regions prone to clipping provides critical insights for the stability and manufacturability of bispecific antibodies incorporating such linker sequences.