Dr. Ansell on the Development of Potential Immune-Harnessing Therapeutics in Lymphoma

Stephen M. Ansell, MD, PhD, professor of medicine, interim chair, Department of Oncology, chair, consultant, Division of Hematology, Department of Internal Medicine, chair, Faculty Development and Recruitment, Mayo Clinic, highlights several emerging therapeutics that have the potential to better harness the immune system in patients with lymphoma subtypes. 

Immunotherapy continues to revolutionize the treatment of patients with lymphoma, Ansell begins. CAR T-cell therapy targeted to CD19 has shown significant promise in lymphoma, Ansell says. This drug class has been shown to induce high rates of remission in B-cell lymphomas, and an increasing body of evidence supports the use of therapies such as lisocabtagene maraleucel (liso-cel; Breyanzi) and axicabtagene ciloleucel (axi-cel; Yescarta) in the second- and third-line settings. These approaches are now being utilized to target other molecules, potentially expanding the agents’ role in the treatment paradigm, Ansell states. 

Additionally, BCMA-directed bispecific antibodies, particularly those targeting CD20 and CD3, have exhibited high efficacy and are currently undergoing development with a broader scope, Ansell continues. These agents are being modified to target multiple immune checkpoints and engage different immune cells, potentially enhancing their therapeutic effect, Ansell details. Novel therapies focusing on the innate immune system, such as macrophages, are also under exploration alongside CD47-targeted treatments, Ansell adds. However, investigators are still awaiting long-term outcomes with these approaches, and there remains uncertainty regarding the efficacy of CD47-targeted therapies, he notes.

Overall, the emphasis of ongoing research in this sphere is to better understand the mechanisms by which the immune system can be effectively engaged across hematologic malignancies, Ansell states. These innovative approaches could not only bolster the immune system primarily through T-cell responses, but may also aid in producing innate immune responses, Ansell emphasizes. As research progresses, these strategies are expected to refine and potentially offer significant clinical benefits, he concludes.