On April 8, 2022 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that preclinical data on its product candidate UCART20x22 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Cellectis, APR 8, 2022, View Source [SID1234611708]). The data showed robust pre-clinical proof of concept with the potential to overcome common mechanisms of resistance to CAR T-cell therapies in relapsed or refractory Non-Hodgkin Lymphoma (r/r NHL), such as single-antigen escape or tumor heterogeneity.
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UCART20x22 is Cellectis’ first allogeneic dual CAR T-cell product candidate being developed for patients with r/r NHL. It features TALEN-mediated disruptions of the TRAC gene (to reduce the risk of graft-versus-host disease) and of the CD52 gene (to permit use of a CD52-directed monoclonal antibody in patients’ preconditioning) to enhance CAR T engraftment, expansion and persistence.
Dual targeting of CD20 and CD22, both validated targets in B-cell malignancies, is designed to enhanced tumor cell killing and to prevent immune escape due to single-antigen targeting. UCART20x22 has the potential to offer an alternative to CD19-directed therapies and CD19 negative relapses.
The poster presentation at AACR (Free AACR Whitepaper) highlighted the following preclinical data:
UCART20x22 showed strong activity against tumor cell lines expressing either a single antigen, CD20 or CD22, or both simultaneously.
In vivo pre-clinical models demonstrate that UCART20x22 efficiently eradicates tumors expressing both or either antigen, and sustained presence of UCART20x22 cells was observed in the bone marrow after tumor clearance.
In vitro assays against primary cells from Non-Hodgkin Lymphoma patients with diverse CD22 and CD20 antigen levels demonstrate that UCART20x22 has potent and specific cytotoxic activity.
"We are very excited to share these encouraging preclinical data at AACR (Free AACR Whitepaper) that support the transition of UCART20x22 into the clinic. Cellectis’ UCART20x22 further validates CD20 and CD22 targets in B-cell malignancies, provides an opportunity to overcome some of the current challenges, and represents a potential therapeutic alternative to CD19-directed therapies. Moreover, manufacturing UCART20x22 from healthy donors holds the potential of an allogeneic CAR T-cell option for r/r NHL patients with enhanced activity." said Beatriz Aranda Orgilles, Ph.D., Team Leader, Immuno-Oncology at Cellectis.
UCART20x22 is expected to be Cellectis’ first product candidate fully designed, developed and manufactured in-house, showcasing the Company’s transformation into an end-to-end cell and gene therapy platform from discovery, product development, GMP manufacturing, to clinical development.
An Investigational New Drug application (IND) for UCART20x22 is expected to be filed this year.
Title: UCART20x22: First allogeneic dual CAR T-cell therapy for the treatment of B-cell malignancies
Date: April 10, 2022 at 1:30 p.m. ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 36
Session Title: Adoptive Cell Therapy 1
Poster Board Number: 5
Abstract Number: 551
E-posters will be available on the AACR (Free AACR Whitepaper) website to registrants of the AACR (Free AACR Whitepaper) Annual Meeting at 1:00 p.m. EDT on Friday, April 8, linked here.