Each episode, ranging from 16 to 48 minutes, provides an inside look into the Company's current and new product candidate pipeline, and manufacturing and technologies.
To watch a replay of all Cellectis Innovation Days episodes, click here.
'For the past four years, in addition to the clinical development of UCART22, UCARTCS1 and UCART123, we have been pushing forward the development our new pre-clinical UCART product candidates, venturing for the first time into the solid tumor space. Additionally, we are thrilled to announce
To date, more than 120 patients have been administered allogeneic CAR T cells utilizing technology developed by
UCARTCS1 in patients with relapsed/ refractory multiple myeloma (r/r MM)
Early preliminary data validates CS1/SLAMF7 as a target for allogeneic CAR-T cells in multiple myeloma. UCARTCS1 expansion and persistence was observed and correlated with anti-myeloma activity, and changes in serum cytokines. The
The
UCART22 in patients with relapsed or refractory B cell acute lymphoblastic leukemia (r/r B-ALL)
BALLI-01 is a phase 1 trial evaluating UCART22 at escalating dose levels in patients with r/r B-ALL.
At the 62nd
Early preliminary data on a small number of patients who received UCART22 after fludarabine and cyclophosphamide pre-conditioning support proof of concept for the use of allogeneic CAR-T products targeting UCART22 in this setting.
UCART22 demonstrated preliminary anti-leukemic activity with no unexpected toxicities in heavily pre-treated patients with ALL, establishingiproof of concept for this product candidate. Importantly, patient T cell recovery happened early in the treatment period, suggesting that the addition of alemtuzumab to the fludarabine and cyclophosphamide lymphodepletion regimen in order to prolong host T-cell suppression should allow for expansion and persistence of UCART22. These cohorts are currently enrolling.
The BALLI clinical study protocol allows for up to 30patients to enroll in the dose escalation period and 53patients in the dose expansion period of the Phase 1/2a. The BALLI-01 trial is currently enrolling patients at DL2i in the dose escalation of the
UCART123 in patients with relapsed or refractory acute myeloid leukemia (r/r AML)
AMELI-01 is a phase 1 trial evaluating UCART123 at escalating dose levels in patients with r/r AML.
Similar to the BALLI-01 trial, AMELI-01 employs a modified toxicity probability interval (mTPI) dose escalation design to evaluate progressive dose levels of UCART123 in concert with fludarabine and cylophosphamide or fludarabine, cyclophosphamide, and alemtuzumab lymphodepletion regimens in patients with r/r AML.
The AMELI-01 clinical study protocol allows for up to 22 patients to enroll in the dose escalation period and 18-37 patients in the dose expansion period of the Phase 1. The AMELI-01 study is active at DL2i of the
UCART20x22 ; the first allogeneic dual CAR T-cell candidate product for B-cell malignancies
A derivative of UCART22, that newly includes an additional CAR targeting CD20.
An allogeneic dual CART targeting both CD20 and CD22, both of which are highly expressed in B-cell malignancies.
UCART20x22 adds CD20 CAR to UCART22 to increase breadth of antigen targeting; targeting two antigens simultaneously could lead to increased efficacy.
Targeting both CD20 and CD22 is more likely to prevent tumor escape and is an alternative to approved autologous CART products targeting CD19.
UCART20x22 uses TALEN to disrupt the CD52 and TRAC genes, similar to UCART22 and UCART123 - thus bearing three genetic edits in total.
Preclinical data show that UCART20x22 is able to kill tumor cells bearing CD20 even in the absence of CD22 antigen.
UCARTMESO for mesothelin-expressing solid tumors
UCARTMESO is an allogeneic CAR T-cell product candidate targeting mesothelin.
Mesothelin is a tumor-associated antigen that is highly and consistently expressed in mesothelioma and pancreatic cancer, and is also over-expresed in subsets of other solid tumors (ovarian cancer, non-small cell lung cancer, gastric cancer, triple-negative breast cancer).
Four gene edits are made: TGF receptor (TGFBR2) knockout for resistance to immunosupressive microenvironment; TCR knockout to prevent graft versus host disease; CD52 knockout to confer resistance to a lymphodepleting CD52 monoclonal antibody and mesothelin CAR lentiviral transduction.
Preclinical data shows that TGFBR2-edited MESO CAR T-cells, exhibit high anti-tumor activity in vitro and in vivo.
Targeting TGF signaling could be beneficial for multiple solid tumors.
UCARTMUC1 for Mucin 1-expressing epithelial cancers
UCARTMUC1 is an allogeneic CAR T-cell targeting Mucin 1 for triple negative breast cancer and a variety of epithelial cancers. As other solid tumor targets can be plagued by safety concerns due to off-tumor expression, MUC1 is of high interest as its expression in normal epithelium is restricted to apical membranes. Additionally, its heavy glycosylation in normal tissue renders MUC1 undetectable by
UCARTMUC1 incorporates three TALEN knockouts (TCR, B2M, and PD-1) with two knockins (IL-12 and HLA-E). In lieu of the deleted beta-2 microglobulin gene (part of MHC-1 complex),
In lieu of the PD-1 gene,
Preclinical data indicates that UCARTMUC1 shows strong intratumoral expansion translating into promising preclinical anti-tumor activity in vivo.
UCARTFAPtargeting Cancer Associated Fibroblasts (CAFs) in the tumor microenvironment
CAFs secrete a number of factors amounting to physical and chemical barriers preventing T-cell activity; reducing the amount of CAFs, will, in turn reduce the immunosuppressive signals emitted from the tumor and hopefully convert 'cold' tumors into 'hot' tumors that can then be targeted with checkpoint inhibitor therapy.
By targeting the cancer-associated fibroblasts,
TCR knocked out to prevent GVHD and beta-2 microglobulin knocked out to provide resistance to the patient's own T-cells.
Investment in GMP manufacturing facilities provides
The first UCART training run (from starting cells to vialed drug product) was completed in
After engineering runs for two different products, the first GMP clinical material is planned to be manufactured by the end of this year.
Additionally,
HEAL is a new gene editing platform developed by
.HEAL highlights lead product candidate TALGlobin01, an autologous ex vivo TALEN-edited CD34+ HSC therapy for the treatment of SCD.
TalGlobin-01 is developed with TALEN technology to induce a double DNA strand break at the SCD-causing HBB gene and AAV particles containing a DNA repair template designed to correct the faulty HBB gene via endogenous homology directed repair (HDR). Under its current setting, this approach promotes about 60% HDR-mediated HBB gene correction and less than 20% of HBB gene inactivation in SCD patient HSPCs in vitro. This genetic correction has led to a sharp decrease of Sickle Hemoglobin (HbS) frequency from 90% to 20% and an increase of up to 80% of functional hemoglobin frequency after erythroid differentiation of corrected HSPCs in vitro.
In vivo preclinical study showed that corrected HSPCs engrafted in the bone marrow of NSG mice and maintained up to 35% of HBB gene correction, 16 weeks post transplantation.
Lysosomal storage disorders (LSD)
This editing strategy opens new avenues for the treatment of LSDs, as it would allow to address the systemic lack of lysosomal enzyme activity, including in the brain, and could be used to produce virtually any defective LSD enzyme. It represents a new platform, in which a single safe and well characterized TALEN could be used to treat different LSDs.
RAG1 SCID
RAG1 is an essential enzyme temporarily expressed in the early development of T and B cells, making traditional gene therapy approaches challenging in terms of spatio-temporal control.
Hyper IgE syndrome
Still in collaboration with Pr. Toni Cathomen (
Contact:
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