Marco Ruella, MD, of Perelman School of Medicine and Scientific Director of the Lymphoma Program, University of Pennsylvania, commented on this study on CD58 aberrations: “This is a very important study because it describes a possible new mechanism for relapse after CAR-T19 immunotherapy in lymphoma. Mutations or reduction in CD58 in non-Hodgkin lymphoma cells clearly correlated with outcomes in patients treated with axicabtagene ciloleucel. This was validated in preclinical models,” Dr. Ruella explained.
Marco Ruella, MD
“Indeed, this study proposes that the CD58-CD2 axis is an important therapeutic target for next-generation chimeric antigen receptor [CAR] T-cell strategies. Some key questions remain to be answered, in particular, the clinical role of CD58 aberrations in other CAR-T19 products besides axicabtagene ciloleucel, such as tisagenlecleucel or lisocabtagene maraleucel, and in other diseases such as acute lymphocytic leukemia, myeloma, or solid cancers. The authors showed that the addition of CD2 co-stimulation in trans in CAR T cells enhanced an antitumor effect in preclinical models,” Dr. Ruella continued.
“Of course, the best clinical strategy to overcome these defects should be explored further. Ongoing clinical trials with CD2-stimulated CAR T-cell therapies and future clinical trials will help to address these important questions,” he said.
DISCLOSURE: Dr. Ruella has served as a consultant to AbClon, BMS, Bayer, and NanoString; has received patents and royalties from UPenn/Novartis; and has received research funding from AbClon.
Engineering chimeric antigen receptor (CAR) T cells to overcome CD58 loss may be a way to boost responses in patients with diffuse large B-cell lymphoma (DLBCL) who do not respond to treatment with axicabtagene ciloleucel and other CAR T-cell therapies, according to a study presented at the 2020...