Manufacturing

Cellectis’ in-house GMP manufacturing facilities provide the company with independence and control over its gene and cell therapy processes, development and production

Our manufacturing process produces product candidates using Universal Chimeric Antigen Receptor T-cells (UCAR T cells), that target cancer cells. Our approach is allogeneic, meaning our UCART product candidates are made from thoroughly tested healthy donor T-cells, unlike autologous CAR T cell products, which are derived from individual patient samples and can be used in that individual patient only.

This off-the-shelf strategy allows for scalability, while maintaining a high quality of T-cells. Our approach also takes advantage of batch manufacturing, which could benefit patients all over the world.  

Cellectis Proprietary Manufacturing Process

With years of experience in allogeneic CAR T manufacturing, we have utilized our validated TALEN® gene-editing technology and process development capabilities for the scalable manufacturing of our UCART product candidates.

In addition, our process – powered by TALEN® and our proprietary PulseAgile electroporation technologies – inactivates targeted genes in a highly efficient and precise manner that avoids harming T-cells during processing. As a result, we can manufacture quality UCART products with high yields.

The Competitive Advantage of in-house Manufacturing

Cellectis is one of the few end-to-end gene-editing, allogeneic CAR T cell company that controls its gene and cell therapy process from start to finish. We are capable of moving an innovative new idea from innovation to development, manufacturing, clinical trials, and delivery directly to the patient – all in-house.

Having our internalized manufacturing ensures clinical program timelines can be readily met with drug product supply so patients are never waiting to be treated. 

Cellectis New York

Innovation, Clinical Development 

  • 25,000 sq ft. facility in New York, New York 
  • Gene editing platform – TALEN® 
  • I/O discovery platform 
  • Gene therapy discovery platform 
  • Clinical development 

Cellectis GMP Paris

Starting Materials for Manufacturing Operations  

  • 55,000 sqft facility in Paris, France
  • Production of starting materials (cell banks, plasmids as well as mRNAs and vectors)  
  • Process and analytical development, QC labs, warehouse cryogenic storage rooms 

Cellectis GMP Raleigh

Clinical & Commercial UCART Manufacturing Operations  

  • ~82,000 sqft facility in Raleigh, North Carolina
  • UCART production suites, filling suite, QC Labs, warehouse, temperature controlled GMP storage including cryogenic storage vessels for incoming donor cells and UCART drug product 

Manufacturing process

  1. Step 1: Frozen Leukopaks

    Blood is drawn from pre-selected donors. Red blood cells and platelets are filtered out leaving only the white blood cells or Peripheral Blood Mononuclear Cells (PBMCs) behind. This is then put into freezer bags which we call leukopaks. 

  2. Step 2: Thawed PBMCS

    The manufacturing process begins by thawing the frozen cells and selectively activating the T-cells.

  3. Step 3: Lentivector Transduction

    Chimeric antigen receptors (CAR) are engineered receptors that allow cells to bind to specific proteins. These are added to the T-cells with the help of lentiviral vector transduction, a virus-derived tool used to penetrate cells.

  4. Step 4: TALEN-Mediated Gene Editing

    Our proprietary Pulse Agile electroporation technology uses precise electrical pulses to create temporary pores in the CAR T-cells that make them permeable. This allows us to introduce the TALEN® (transcription activator-like effector nucleases), which are enzymes that have been engineered to cut specific sequences of DNA. As an example, a precise edit is made that eliminates the T-cell receptor (TCR). This is an important step since the TCR would normally trigger a rejection response from the patient’s immune system since the cells come from donors. Knock-outs of more than one gene are possible with our technologies.

  5. Step 5: Cell Expansion

    The population of gene-edited CAR T-cells is amplified using automated processes and special tools called bioreactors. This part of the process is also referred to as cell expansion. 

  6. Step 6: Purification

    Gene-edited CAR T-cells are sorted and selected through our purification processes.

  7. Step 7: Fill and Finish

    Vials are filled with our allogeneic UCART product candidates. The formulation includes a  cryopreservation medium, which allows the cells to be preserved at very low temperatures for an extended shelf-life.

  8. Step 8: Frozen UCART Product

    The vials are frozen and packaged so that they can be safely shipped to hospitals for administration to patients.

Quality control checks are done all throughout the manufacturing process (in-process controls). These continuously assess the UCART product candidates on four key attributes: identity, safety, strength and stability.