Cryopreserved anti-CD22 and bispecific anti-CD19/22 CAR T cells are as effective as freshly infused cells

Alexandra Dreyzin; Sandhya R Panch; Haneen Shalabi; Bonnie Yates; Steven L Highfill; Ping Jin; David Stroncek; Nirali N Shah

doi:10.1016/j.omtm.2022.12.004

Cryopreserved anti-CD22 and bispecific anti-CD19/22 CAR T cells are as effective as freshly infused cells

Mol Ther Methods Clin Dev. 2022 Dec 7:28:51-61. doi: 10.1016/j.omtm.2022.12.004. eCollection 2023 Mar 9.

Authors

Alexandra Dreyzin¹, Sandhya R Panch², Haneen Shalabi³, Bonnie Yates³, Steven L Highfill⁴, Ping Jin⁴, David Stroncek⁴, Nirali N Shah³

Affiliations

¹ Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC 20010, USA.
² Division of Hematology, Hutchinson Cancer Center, University of Washington, Seattle, WA 98109, USA.
³ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Department of Transfusion Medicine and Cellular Engineering, Center for Cellular Engineering, NIH Clinical Center, NIH, Bethesda, MD 20892, USA.

Abstract

Cryopreservation of chimeric antigen receptor (CAR) T cells facilitates shipment, timing of infusions, and storage of subsequent doses. However, reports on the impact of cryopreservation on CAR T cell efficacy have been mixed. We retrospectively compared clinical outcomes between patients who received cryopreserved versus fresh CAR T cells for treatment of B cell leukemia across two cohorts of pediatric and young adult patients: those who received anti-CD22 CAR T cells and those who received bispecific anti-CD19/22 CAR T cells. Manufacturing methods were consistent within each trial but differed between the two trials, allowing for exploration of cryopreservation within different manufacturing platforms. Among 40 patients who received anti-CD22 CAR T cells (21 cryopreserved cells and 19 fresh), there were no differences in in vivo expansion, persistence, incidence of toxicities, or disease response between groups with cryopreserved and fresh CAR T cells. Among 19 patients who received anti-CD19/22 CAR T cells (11 cryopreserved and 8 fresh), patients with cryopreserved cells had similar expansion, toxicity incidence, and disease response, with decreased CAR T cell persistence. Overall, our data demonstrate efficacy of cryopreserved CAR T cells as comparable to fresh infusions, supporting cryopreservation, which will be crucial for advancing the field of cell therapy.

Keywords: CAR T; CAR T expansion; CAR T manufacturing; cell therapy; clinical outcomes; cryopreservation; cytokine release syndrome.