Dr Bretjens on Efforts to Expand CAR T-Cell Therapy Beyond B-Cell Malignancies

“[The] most important to realize [here] is that the indications for [CAR T-cell therapies] that are FDA approved are all in the context of B-cell malignancies, which means that there is an entire field of myeloid malignancies, [such as] acute myeloid leukemia, where we still have to fundamentally find good targets on the surface of those tumor cells, as opposed to targeting B-cell lymphoid tumors.”

Renier Brentjens, MD, PhD, hematologist/oncologist, deputy director, Chair, Department of Medicine, The Katherine Anne Gioia Endowed Chair in Cancer Medicine, Roswell Park Comprehensive Cancer Center, discusses the current landscape of CAR T-cell therapy and ongoing efforts to expand its application beyond B-cell malignancies. These insights were shared at the 2024 ASH Annual Meeting.

Brentjens notes that all current FDA-approved CAR T-cell therapies within the hematologic field are indicated for patients with B-cell–derived malignancies, including acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma, and more. These therapies target antigens such as CD19, CD22, and BCMA, which are uniquely and consistently expressed on malignant B cells. He explains that these targets have facilitated the successful utilization of CAR T-cell therapy for patients with relapsed/refractory B-cell malignancies.

However, translating this treatment class to myeloid malignancies, such as acute myeloid leukemia (AML), has presented significant challenges, Brentjens continues. Unlike B-cell malignancies, myeloid cancers lack tumor-specific antigens that are uniquely expressed on the cancer cells. Brentjens notes that these challenges have necessitated innovative strategies to safely target myeloid malignancies.

Efforts are underway to overcome these obstacles, Brentjens shares. Emerging technologies, such as logic-gated CAR T cells, are being explored to enhance antigen specificity by requiring recognition of multiple markers before activating the CAR T cells, he continues. Further investigation into novel antigens expressed in myeloid malignancies may provide greater selectivity for targeting these cancer cells, and these advancements could help address the inherent limitations of CAR T-cell therapy in myeloid malignancies, Brentjens concludes.