IO360: first allogeneic dual CAR-T shows promise in B-cell Non-Hodgkin lymphoma

Autologous chimeric antigen receptor (CAR) T-cell therapies have proven to be groundbreaking in the management of select hematologic malignancies. Despite their notable efficacy, prolonged observation of patients treated with CD19 or CD20 CAR T-cells has illuminated instances of relapse, often linked to antigen loss. The therapeutic avenues available post-CAR T-cell relapse are notably limited, underscoring the pressing need for the development of novel modalities to augment current survival outcomes. Addressing this unmet need, Cellectis’s UCART20x22 represents a pioneering allogeneic dual CAR T-cell product candidate designed to target two established antigens within B-cell malignancies, CD20 and CD22.

At the 10th Annual Immuno-Oncology 360° (IO360) conference, held 27–29 February, results were presented from the Phase I/IIa NATHALI-01 clinical trial evaluating UCART20x22 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). As of 1 July, 2023, three patients had been enrolled and treated at dose level 1 (50 million cells). At Day 28, every patient exhibited a response, including one instance of partial metabolic response and two instances of complete metabolic responses among those who had previously failed autologous CD19 CAR T-cell therapies. All patients experienced mild to moderate cytokine release syndrome (CRS), which resolved following treatment. There were no cases of immune effector cell-associated neurotoxicity or graft-versus-host disease, and no dose-limiting toxicities were observed with UCART20x22. The expansion of UCART20x22 was associated with increased levels of serum cytokines and inflammatory markers, as well as CRS.

The NHL cell and gene therapy market is forecast to be worth $8.2 billion in the eight major markets (8MM US, France, Germany, Italy, Spain, UK, Japan, and China) by 2029, as per GlobalData’s sales and forecast database. According to GlobalData’s epidemiology report, there were over 550,000 diagnosed prevalent cases of B-NHL in the US in 2023, thus evincing a large addressable market. However, competition in the space is fierce, with notable competitors including Kymriah (tisagenlecleucel) and Breyanzi (lisocabtagene maraleucel). Nonetheless, one of the major advantages that sets UCART20x22 apart is its ability to target two antigens at the same time; CD19-targeted therapies focus on a single molecule, often leading to relapse when tumours lose CD19 expression. With UCART20x22 treatment, even if one antigen is lost, the presence of a second antigen ensures continued recognition and elimination of tumour cells. Furthermore, UCART20x22 is engineered to be readily accessible off-the-shelf, providing a viable remedy for patients with compromised T-cell functionality or instances of failed autologous manufacturing processes.