UCART20x22

TALEN® gene editing technology is used to inactivate the TRAC and CD52 genes to minimize graft-versus-host disease (GvHD) and allow for the use of alemtuzumab (CLLS52, an anti-CD52 monoclonal antibody) in the lymphodepletion (LD) regimen, respectively...After LD with FCA (fludarabine 30 mg/m2 × 3d, cyclophosphamide 0.5g/m2 × 3d, CLLS52 12 mg on D1, 24 mg on D2, D3), a single infusion of UCART20x22 is administered at a flat dose level ([DL1] 50 x 106 cells; [DL2] 150 x 106 cells; and [DL3] 450 x 106 cells)...Pt 3 is an 18yo female with R/R DLBCL transformed from marginal zone lymphoma who previously received chemoimmunotherapy, venetoclax, ibrutinib, BR, CAR19, obinutuzumab, glofitamab, tafasitamab, lenalidomide, and an experimental epigenetic modifier...Pt 1 had G1 CRS and received tocilizumab (toci) x3 and dexamethasone (dex) x1... As of 01 July 2023, 3 pts were enrolled and treated at DL1. Pt 1 is a 76yo female with double-expressor diffuse large B-cell lymphoma (DLBCL) relapsed after R-CHOP, radiation therapy, and polatuzumab vedotin with bendamustine/rituximab (BR) and was considered ineligible for CAR19 due to recent high dose bendamustine. Pt 2 is a 65yo female with R/R triple-hit lymphoma transformed from follicular lymphoma who was previously treated with radiation therapy, BR, dose-adjusted R-EPOCH, and two separate CAR19 treatments.

P1/2, N=80, Recruiting, Cellectis S.A. | Not yet recruiting --> Recruiting

P1/2, N=80, Not yet recruiting, Cellectis S.A.

TALEN® gene editing technology was used to mediate inactivation of the TRAC and CD52 genes : TRAC KO is used to prevent Graft-vs-Host Disease , and CD52 KO to allow deepe r host lymphocyte depletion by confer ring resistance to lymphodepletion regimens including an anti-CD52 monoclonal antibody, such as alemtuzumab . Furthermore , in vitro assays against primary cells from Non-Hodgkin Lymphoma patient s with diverse CD22 and CD20 antigen levels demonstrate that UCART20x22 has potent and specific cytotoxic activity as well as IFN g release against these panel of samples . Conclusion W e present a robust pre-clinical proof of concept of a potent allogeneic dual CAR T-cell product candidate , UCART20x22, with the potential to 1) overcome common mechanisms of resistance in B- NHL, 2) enable the development of allogeneic CART option for B-NHL patients, 3) reduce the time from treatment decision to infusion.

Besides efficiently targeting two commonly expressed antigens in B-cell malignancies, UCART20x22 incorporates TALEN® mediated TRAC and CD52 specific gene editing to prevent Graft-vs-Host Disease and improve persistence in the presence of alemtuzumab (an anti-CD52 monoclonal antibody that can be used as part of a lymphodepleting regimen). These attributes allow the production of allogeneic CAR T-cells from healthy individuals that can be administered at the time of treatment decision. In summary, we show an efficient first in class allogeneic dual CAR T-cell product candidate with demonstrated in vitro and in vivo properties to overcome antigen escape in B-cell malignancies.