­Are bispecific T-cell engagers (BiTEs) “better” than CAR T-cells? Authors argue both sides of this question in the January 26, 2021, issue of Blood Advances.

Marion Subklewe, MD, of the University of Munich in Germany, identifies several “significant advantages” for BiTEs, including:

• They are off-the-shelf products with a high safety profile, offering both dose titration and escalation.
• They are particularly promising against early-stage disease with low tumor burden and a still-functional T-cell compartment. 
• They offer the flexibility of targeting multiple antigens both simultaneously and sequentially.
• They can be used in combination with chemotherapy, small molecules, and immunomodulatory drugs such as checkpoint inhibitors.

John C. Molina, MD, and Nirali N. Shah, MD, of the National Cancer Institute’s Center for Cancer Research, argue for the superiority of CAR T-cells, noting that:

• In clinical trials, CAR T-cells have achieved higher rates of complete and MRD-negative remission than blinatumomab, the only BiTE that to date has received FDA approval.
• CAR T-cells have shown greater efficacy than blinatumomab in patients with both higher disease burden and extramedullary disease.
• The CAR T-cell therapy tisagenlecleucel was deemed more cost effective than blinatumomab based on a higher estimate for quality-adjusted life years (11.26 for the CAR T-cell therapy versus 2.25 for the BiTE).
• CAR T-cells have demonstrated tolerability in an older, heavily pretreated, chemotherapy-refractory population.

Both sides ultimately agree that there is a clinical role for both BiTEs and CAR T-cell therapies and that patients are sequentially using both modalities as personalized individual treatments.

– Molina JC, Shah NN. CAR T cells better than BiTEs. Blood Adv. 2021;5(2):602-606. doi:10.1182/bloodadvances.2020003554

– Subklewe M. BiTEs better than CAR T cells. Blood Adv. 2021;5(2):607-612. doi:10.1182/bloodadvances.2020001792

Tags: CAR-T, Therapy, BiTEs, engagers, cancer