Matthew Frank, MD, PhD, on Tackling Antigen Loss and Absence in Hematological Malignancies

“We know that antigen loss is a problem... One [potential solution] could be to just simply look at antigen levels. If you have no CD19, but you have CD20 and CD22, maybe we go after those antigens... [In other cases], maybe we want to use combinations. We have a lot of emerging CD19/CD20[-targeted therapies and] there are triples now: CD19/CD20/CD22...”

Many chimeric antigen receptor T-cell (CAR-T) therapies function by targeting a single antigen commonly expressed by the cancers they are intended to treat. Although in some cases this approach can be highly effective, if the cancer cells do not express or lose expression of the targeted antigen then the CAR-T product’s efficacy may be dramatically reduced or nullified. With this in mind, many companies and investigators are currently looking into various methods of overcoming this challenge.

Matthew J. Frank, MD, PhD, assistant professor of medicine in the Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University, presented a study called “CD22 CAR T cell therapy is safe and effective in patients with large B cell lymphoma who have relapsed after CD19 CAR T cell therapy” at the European Hematology Association (EHA) 2023 Congress, held June 8-11, both virtually and in Frankfurt, Germany. His presentation covered findings from a phase 1 clinical trial (NCT04088890) evaluating the investigational CD22-directed CAR-T therapy CAR22 in adults with relapsed/refractory B-cell malignancies. 

In an interview with CGTLive™’s sister publication OncLive™, Frank discussed the topic of antigen loss and absence more broadly and touched on several possible methods for addressing this problem that investigators in the CAR-T space are currently exploring. Notably, he discussed the limitations of immunohistochemistry for detecting antigen expression in the first place and stressed the need for new detection technologies. He additionally spoke about the potential of CAR-T therapies that target multiple antigens with each individual CAR T-cell versus the potential of combination therapies that include multiple different types of CAR T-cells that each target different antigens. Frank also answered a question about the inclusion of a patient without CD22-expression in the phase 1 trial.

Click here for more coverage of EHA 2023.

REFERENCE
Frank M, Baird J, Kramer A, et al. CD22 CAR T cell therapy is safe and effective in patients with large B cell lymphoma who have relapsed after CD19 CAR T cell therapy. Presented at: the European Hematology Association (EHA) 2023 Congress, June 8-11, held both virtually and in Frankfurt, Germany. Abstract #S230