News

Article

Cellectis Describes Novel CAR-T Design in New Paper

Author(s):

Researchers from Cellectis investigate how external signals in the tumor microenvironment could control the cell-surface expression and specificity of engineered CARs.

Beyond challenges related to expansion and persistence of T-cell therapies, there are also challenges related to overall toxicity, specificity, and safety of T-cell therapies. Advances have been made to arm T-cell therapies with suicide switches or marker genes to prevent on-target, off-tumor activity. Bispecific T-cells, which often have an inhibitory CAR recognizing antigens on normal tissues and an activating CAR to recognize tumor antigens, are also in development.

A new, locally effective CAR-T construct was the focus of a

new paper

published on Jan. 23, 2017 in Scientific Reports. Researchers from Cellectis engineered T cells to respond to variation in oxygen levels, enabling the immune cells to remain inactive in normoxic conditions and become active in low-oxygen (hypoxic) settings, such as the conditions that are characteristic of the tumor microenvironment.

The cells were created to contain an oxygen-sensitive subdomain of hypoxia-inducible factors 1-alpha (HIF1α), a protein that degrades in normal oxygen environments and stabilizes (i.e., becomes active) in the presence of low oxygen levels. The subdomain acts as a sensor to control T-cell response, making the construct safer to normal tissues. Thus, the construct’s cytolytic ability is directly tied to level of oxygen in the local environment.

Allogeneic therapies in the pipeline

Although off-the-shelf, gene-edited chimeric antigen receptor T-cell therapies (CAR-T therapies) are ideal for the manufacture of cell therapies at large scale, and are associated with a lower risk of graft-versus-host disease in patients upon adoptive transfer, there hasn’t been much action on the regulatory front for these universal cell therapies-until now. Cellectis

announced in early January 2017

that an investigational new drug application (IND) for its T-cell candidate targeting CD123 was filed with FDA, and according to the company, it is the first allogeneic CAR-T being investigated in human clinical applications in the United States.

The universal CAR-T (UCART) UCART123 will enter into Phase I trials during the first part of 2017. Cellectis will test the agent’s efficacy to target CD123, the membrane biomarker that is typically overexpressed on the cells of patients with acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN), and other hematologic malignancies.

Sources: Scientific Reports, Cellectis

Newsletter

Get the essential updates shaping the future of pharma manufacturing and compliance—subscribe today to Pharmaceutical Technology and never miss a breakthrough.

Related Videos
A global supply chain map, visualizing the complex network of transportation routes and distribution centers | Image Credit: © venusvi - stock.adobe.com
Shortcut from point A to point B | Image Credit: © Olivier Le Moal - stock.adobe.com
Behind the Headlines, Episode 21: Waters-BD Merger, Merck’s $10B Bet, and Biotech’s Investment Frontiers
Wooden blocks spelling TARIFFS are placed on a map of North America, specifically over the United States and Mexico | Image Credit: © Rokas - stock.adobe.com
Jason Waite, International Trade Expert, Alston & Bird
Simona Guidi, Associate Director, ProPharma
Tore Bergsteiner
Behind the Headlines, Episode 20: CAR-T Milestones, Abbvie and Eli Lilly M&A Moves, and More
Related Content