Posts Tagged ‘UCART19’

UPDATED: CAR-T Therapy in Leukemia

Curator: Larry H. Bernstein, MD, FCAP

UPDATED 3/15/2020

UCART19: First in Man Proof of Concept to be Presented at 2015 ASH Annual Meeting

November 05, 2015


New York, November 5, 2015Cellectis (Alternext: ALCLS – Nasdaq: CLLS) today announced that Great Ormond Street Hospital (GOSH) and University College London (UCL)  will present encouraging data from a first in man clinical use of UCART19, at the 57th American Society of Hematology (ASH) Annual Meeting in Orlando during the poster session.
GOSH has treated in June 2015 a young leukemia patient under a special license from theMedicines & Healthcare products Regulatory Agency (MHRA) with Cellectis’ TALEN® gene edited allogeneic UCART19 product candidate because no other therapies were available for refractory relapsed Acute Lymphoblastic Leukemia (ALL) following mismatched allogeneic stem cell transplantation.
In response to an unsolicited request from Professor Waseem Qasim, Consultant Immunologist at GOSH and Professor of Cell and Gene Therapy at University College London (UCL) Institute of Child Health, Cellectis gave its approval for the use of its UCART19 product candidate and technologies under GOSH’s “Specials” license and responsibility, for the particular clinical needs of that individual patient.
Professor Qasim says: “The successful treatment of a patient with UCART19 cells represents a landmark in the use of new gene engineering technology. If replicated in other patients, it could represent a huge step forward in treating leukaemia and other cancers.”

An infant in London with an aggressive leukemia has been given TALEN-edited immune cells, a treatment that appears to have put her disease into remission, the Wall Street Journal reports.

The infant, Layla, had relapsed acute lymphoblastic leukemia against which conventional treatment was ineffective. The Journal notes that an experimental treatment called CAR in which patients’ T cells are removed and engineered to better find and eliminate leukemia cells had shown some success in trials. But Layla didn’t have enough of her own immune cells to use.

Instead, clinicians from Great Ormond Street and University College London researchers along with Cellectis turned to T cells from a healthy donor that they edited using TALENs so they didn’t attack the girl’s body as well as so they wouldn’t be attacked by the leukemia drugs then given to the girl.

Weeks after the cells were given to Layla, the Journal reports, she went into remission.

“We are very glad for this young patient to have benefited from our highly innovative TALEN® gene edited allogeneic CAR T therapy UCART19. We expect to accelerate our clinical development of TALEN® gene-edited allogeneic CAR-T therapies to further confirm this encouraging clinical proof of concept,” said Doctor Mathieu Simon, MD, Executive Vice President, Chief Operating Officer at Cellectis.
“Our team aims to provide to patients, with unmet medical needs, access to the first allogeneic CAR-T therapy, UCART19 made with Cellectis’ TALEN® gene-editing technologies,” said Doctor André Choulika, Founder, Chairman and Chief Executive Officer of Cellectis. “Cellectis had, is and will invest significant amounts of energy and creativity to provide cancer patients with an accessible, cost-effective, off-the-shelf allogeneic CAR-T therapies across all geographies. UCART19 has been provided for to a patientwho could not undergo an autologousCAR-T therapy. Our goal is to make our product candidates accessible to anyone.”

First Clinical Application of Talen Engineered Universal CAR19 T Cells in B-ALL

Gene Therapy and Transfer

Program: Oral and Poster Abstracts

Session: 801. Gene Therapy and Transfer:

Poster I Saturday, December 5, 2015, 5:30 PM-7:30 PM

Hall A, Level 2 (Orange County Convention Center)

Waseem Qasim, MBBS PHD1*, Persis Jal Amrolia2*, Sujith Samarasinghe, MD, PhD3*, Sara Ghorashian, MD, PhD, FRCPath1*, Hong Zhan, PhD4*, Sian Stafford, PHD1*, Katie Butler, PHD1*, Gul Ahsan5*, Kimberly Gilmour5*, Stuart Adams, PHD5*, Danielle Pinner5*, Robert Chiesa5*, Steve Chatters, PHD5*, Sue Swift, PHD1*, Nicholas Goulden, MD, PhD3, Karl Peggs, MBBChir, MRCP, FRCPath6*, Adrian J Thrasher, MD, PhD1*, Paul Veys2* and Martin Pule, PhD7*

1 INSTITUTE OF CHILD HEALTH, UCL, London, United Kingdom

2 Bone Marrow Transplantation Department, Great Ormond Street Hospital, London, United Kingdom

3 Department of Haematology, Great Ormond Street Hospital For Children, London, United Kingdom

4 Institute of Child Health / Molecular and Cellular Immunology Unit, University College London, London, United Kingdom


6 CANCER INSTITUTE, UCL, London, United Kingdom

7 Cancer Institute, University College London, London, United Kingdom

About UCART19
UCART19 is a potential best-in-class allogeneic engineered T-cell product for treatment of CD19 expressing hematologic malignancies, initially developed in Chronic lymphocytic leukemia (CLL) and Acute lymphoblastic leukemia (ALL). Servier has an option under the collaboration agreement to acquire the exclusive rights to further develop and commercialize UCART19. Engineered allogeneic CD19 T-cells currently stand out as a real therapeutic innovation for treating various types of leukemia and lymphoma. Cellectis’ approach with UCART19 is based on the preliminary positive results from clinical trials using products based on the CAR technology and has the potential to overcome the limitation of the autologous current approach by providing an allogeneic frozen, “off the shelf” T-cell based medicinal product.
About Great Ormond Street Hospital (GOSH)
Great Ormond Street Hospital for Children NHS Trust is the country’s leading centre for treating sick children, with the widest range of specialists under one roof. With the UCL Institute of Child Health, they are the largest centre for paediatric research outside the US and play a key role in training children’s health specialists for the future.
About the UCL department of hematology
The UCL department of hematology is the major tertiary referral center in the UK for all types of hematological malignancies. They have assumed a global leadership position in stem cell transplantation and adoptive cell therapy for leukemia patients.


UPDATED 3/15/2020

     An article by Jennifer Couzin-Frankel in Science discusses safety profile of early CRISPR gene editing trials in a set of cancer patients.  Two women and one man, all in their 60’s (one with sarcoma and the other two with multiple myeloma received CRISPR altered chimeric antigen receptor T cells (CAR-T) and tolerated the therapy quite well.  The study was led by University of Pennsylvania’s Carl June, M.D., who said the primary goal of the trial was designed to determine safety, not efficacy.  

However the trial also wanted to answer a conundrum which was evident from early CAR-T therapies: that not all patients showed complete response and some who showed initial response could show a relapse.  Therefore the investigators attempted to use CRISPR to knockout certain genes while hoping to prevent the off target effects that is sometimes seen with CRISPR gene-editing (note the problems with some of the Vertex/ CRISPR Therapeutics trials).

The trial criteria were very specific.  Patients tumor cells had to express the protein NY-ESO-1, to which the investigators would target in the engineered T-cells and to boost the immune response they also CRISPRed out the PD-1 protein in the engineered T-cells, thereby releasing the engineered CAR-T from immune block.  Fortunately any off target effects, which were small, decreased to minimal over time and CRSPR-edited cells lasted for 9 months versus only 2 months for conventional CAR-T.  However it appears at this point, due to limited number of patients, although very safe, therapeutic response was limited.


CRISPR Takes on Cancer

Science  07 Feb 2020:
Vol. 367, Issue 6478, pp. 616
DOI: 10.1126/science.367.6478.616



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