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Adoptive immunotherapy is based on infusing a patient with extra functioning immune cells grown from his/her own body (autologous cell therapy) or taken from a donor (allogeneic cell therapy). In the fight against cancer, allogeneic cell therapy offers something the conventional autologous approach cannot: the potential to treat large numbers of patients using a standardized, off the shelf therapeutic product.
Derived from a genetically different donor. Cellectis’ gene-editing technologies allow us to create allogeneic CAR T-cells, meaning they are derived from healthy donors rather than the patients themselves.
Amino acids are substances containing nitrogen and hydrogen. They are referred to as the building blocks of proteins.
An apheresis is a medical technology in which the blood of a person is passed through an instrument that is essentially designed as a centrifuge, where all the components of the blood are separated. One of the separated portions is then withdrawn and the remaining components are retransfused into the person.
In the field of hematology, aplasia is an incomplete or defective development, or cessation of the usual regenerative process leading to a strong decrease of the number of white blood cells, accompanied by a decline in other blood components (red blood cells and platelets). The aplasia often happens as a side effect of some chemotherapy drugs.
Derived from an individual's own tissues, cells, or DNA.
The OECD defines biotechnology as “the application of science and technology to living organisms, as well as parts, products and models thereof, to alter living or non-living materials for the production of knowledge, goods and services.” Biotechnology, or “biological technology” in full, is a cross between biology – the study of life – and a range of technological breakthroughs from specific disciplines such as microbiology, biochemistry, biophysics, genetics, molecular biology, computer science, and more.
CARs or Chimeric Antigen Receptors are engineered molecules that, when present at the surface of T-cells, enable them to recognize specific proteins or antigens that are present on the surface of other cells. These receptors are typically used to graft the specificity of an antibody derived from a single cell, or a monoclonal antibody, onto a T-cell and provide it with a specific targeting mechanism to seek, identify, interact with and destroy the tumor cells bearing a selected antigen associated with that tumor also known as the tumor-associated antigen, or TAA.
Cellectis’ therapeutics programs are focused on developing product candidates using our gene-editing platform to develop genetically modified T-cells that express a Chimeric Antigen Receptors (CAR) and are designed to target and kill cancer cells. Immune cells -most usually T-lymphocytes- can be engineered to express a CAR able to recognize proteins present at the surface of cancer cells. Upon cell-to-cell contact between effector and targeted cells, antigen recognition will activate the effectors, giving them the signal to attack their targets, and leading ultimately to the killing of cancer cells.
CR or Complete Remission (also called Complete Response) is the disappearance of all signs of cancer in response to treatment. It is also referred to as “no evidence of disease” (NED). But this does not always mean the cancer has been cured as some cancer cells can still be in the body but be undetectable.
CRi is a complete remission with incomplete hematologic recovery according to the criterias from the disease it’s been applied to.
In Europe, the Clinical Trial Application (CTA) filing is the regulatory step consisting on the submission of the required study documentation package to the health authority to obtain the authorization to perform clinical investigation. In the European Union, the health autority is The European Medicines Agency (EMA).
Cytokines are a broad and loose category of small proteins that have an important role in cell signaling. A cytokine release syndrome occurs when large numbers of white blood cells, including B-cells, T-cells, natural killer cells, macrophages, dendritic cells and monocytes are activated and release inflammatory cytokines, which in turn activate yet more white blood cells. This is the response of the immune system when fighting pathogens, as cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection. In addition, cytokines activate those cells, stimulating them to produce more cytokines.
DNA is a molecule that occurs in every living cell. It contains all the information necessary for an organism to develop and function. It is also the basis of heredity in that it is passed on, either partially or in full, during reproduction. The genetic blueprint carried by DNA constitutes an organism’s genome.
Invented in the second half of the 1970s, DNA sequencing involves determining the sequence of the nucleotides in a given DNA fragment. The DNA sequence contains all of the information a living organism needs to survive and reproduce. DNA sequencing can be used in medicine to identify, diagnose and possibly find cures for inherited or acquired genetic diseases. In biology, the study of DNA sequences has become a key tool, for example, in detecting defective genes.
After identification of a new potential target, a product candidate or drug candidate is developed based on compounds with strong therapeutic potential.
Or electropermeabilization, is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, RNA or DNA to be introduced into cells.
The European Medicines Agency (EMA) is the European Union agency whose main responsibility is the protection and promotion of public and animal health, through the evaluation and supervision of medicines for human and veterinary use.
An endonuclease is a type of nuclease. Nucleases cut nucleic acids into shorter fragments. Endonucleases can cut through the center of a polynucleotide chain, as opposed to exonucleases which only cleave nucleotides from the ends of the chain.
Enzymes are proteins that speed up (catalyze) reactions inside organisms while themselves remaining unchanged and without altering the substances taking part in the reaction. Without enzymes, certain basic biological reactions would not happen fast enough. Enzymes enable new substances to be synthesized so that cells can form and grow (anabolism). They also help break substances down to provide the body with energy (catabolism).
FCA is a lymphodepletion regimen consisting of fludarabine, cyclophosphamide and an anti-CD52 monoclonal antibody.
The Food and Drug Administration (FDA) is a federal agency of the United States Department of Health and Human Services, responsible for protecting and promoting public health, including through the regulation and supervision of biopharmaceuticals.
A first line patient refers to a patient that has not undergone any previous therapies. In addition, a first line therapy is the first therapy the patient will receive.
A gene is a segment of DNA that provides the blueprint for making some part of a living organism. DNA is the basic constituent of chromosomes, by which all creatures pass on their hereditary traits from parent to offspring. The stretch of DNA that makes up a gene is itself composed of nucleotides. There are 4 types of nucleotides, abbreviated as follows: A (for adenine), T (for thymine), G (for guanine), and C (for cytosine).
Gene correction is used to replace an existing defective sequence (which generally impacts the gene’s functions) with a functional sequence. For example, to treat a serious genetic disease such as cystic fibrosis.
Gene inactivation is used to prevent the expression of a gene. This approach can be used to treat persistent viral infections such as AIDS.
Gene insertion is used to add a new function to the genome. For example, this is used in drug discovery, or in order to overcome a genetic defect like hemophilia.
A genome is the full genetic make up of an individual or species, encoded in its DNA (except for certain viruses which genome is carried by RNA molecules). The genome provides the layout for how cells should function and how hereditary traits should be passed down from one generation to the next. It contains all the coding sequences of DNA (which are transcribed via messenger RNA and translated into proteins) as well as the non coding sequences (which are not translated).
Good Manufacturing Practices (GMP) are a set of regulations applicable to the manufacturing of health products, especially medicines intended for human use, such as UCART product candidates for example. A company is required to comply with GMP regulations in order to be granted a license from governmental regulatory agencies to manufacture pharmaceutical products.
Graft-versus-host disease (GvHD) is a complication which follows an allogeneic tissue transplant, consisting of immune cells in the graft recognizing the recipient as "non-self" and attacking its cells.
A genetic recombination event between two identical sequences located on two different DNA molecules or separated from each other on the same molecule.
In the U.S., the Investigational New Drug (IND) filing is the regulatory step consisting of submitting the required study documentation package to the health authority, the Food and Drug Administration or FDA, to obtain the authorization to perform clinical investigation.
In molecular biology, a knock-in is the introduction of a gene of interest into a given locus. After homologous recombination, the gene of interest is controlled by the target gene’s promoter and regulatory sequences and is therefore synthesized in lieu of the target gene.
In molecular biology, a knock-out (or KO) is the complete inactivation of a gene. As an example, Cellectis uses the knock-out process to inactivate the TRAC gene in T-cells. This gene being responsible for the T-cell recognition of the non-self, Cellectis turns these T-cells into allogeneic T-cells that can be injected to any patient.
Lentiviruses are a subclass of retroviruses. These viruses are made of an envelope, a capsid and, inside, a RNA genome. Lentiviruses have evolved to deliver their genome efficiently to their target cells (including T-cells), where this RNA is reverse-transcribed into a DNA molecule and is then very efficiently integrated into the genome of the cell thanks to the viral integrase enzyme. Lentivectors utilize these interesting natural biological properties of lentiviruses to serve as an efficient gene transfer tool. Lentiviral vector is a crucial technology for CAR T-cell therapies.
Lymphocytes are a type of white blood cells. As part of the immune system, they play a major role in defending the body against infection. They are produced in the bone marrow and circulate through the bloodstream and lymphatic tissues (spleen, lymph nodes).
There are two main types of lymphocytes: B-cells and T-cells. The difference between them is both molecular (they bear different receptors on the surface of the cell) and functional (B lymphocytes produce antibodies while T lymphocytes kill or organize the fight against abnormal or infected cells).
Lymphodepletion is a medical procedure in which certain immune cells are eliminated, e.g. via chemotherapy, to prevent the body from rejecting a transplant of engineered T-cells.
Meganucleases are "molecular DNA scissors" that can be used to replace, remove or modify sequences in a highly targeted way. These proteins are the perfect tools for genome engineering because they are specific enough to home in on and splice a single site per genome. Meganucleases are used to modify all genome types and open up wide avenues for innovation, particularly in the field of human health (for example by removing viral genetic material or "repairing" damaged genes) and in agricultural biotechnology. Meganucleases can be found in many organisms, including archaea (also archaebacteria), bacteria, phages, fungi, yeasts, algae and certain plants.
The minimal residual disease is a measurement of the number of residual leukemic cells that remain after treatment. It is the major cause of relapse in cancer and leukemia.
A mutation is the permanent alteration of a nucleotide sequence of the genome in any organism.
An enzyme capable of catalyzing nucleic acids—RNA (ribonucleic acid) and DNA (deoxyribonucleic acid)—into nucleotides and various components of these nucleic acids. They cut between two nucleotides in a nucleic acid strand.
A nucleotide is a basic component of DNA and RNA. It is a molecule composed of a sugar (ribose or deoxyribose), one to three phosphates and a nucleobase, also known as a nitrogenous base. Certain nucleotides combine to form the basis of DNA and RNA, while others are cofactors or coenzymes. For DNA, there are four different nucleotides, each with a different nitrogenous base:
- dAMP, a purine, which nitrogenous base is adenine (A)
- dGMP, a purine, which nitrogenous base is guanine (G)
- TMP, a pyrimidine, which nitrogenous base is thymine (T)
- dCMP, a pyrimidine, which nitrogenous base is cytosine (C).
Off-site cleavage or off-target genome editing are non-specific and unintended genetic modifications that occur during the gene engineering process.
Partial remission (also known as partial response) is a decrease in the size of the tumor burden, or in the extent of cancer in the body, in response to treatment.
After identification of a new potential target, a product candidate or drug candidate is developed based on compounds with strong therapeutic potential.
This is one of the most important types of molecules and is present in all living organisms and viruses. Proteins perform essential cellular functions, such as the formation of cell architecture and the modulation of cell activity. Proteins are macromolecules that are composed of long chains of amino acids (basic building blocks) and come in various forms, such as enzymes, hormones, receptors and neurotransmitters. Proteins are built from the genetic information contained in a gene.
PulseAgile is our proprietary technology for electroporation. It uses a particularly effective combination of high voltage peaks, that are optimized to create transient holes in the cell membrane, followed by lower voltage pulses that help mRNA migrate into the cells. This technology is optimized to preserve high cell viability and is thus suited for large-scale manufacturing.
Cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment or it may become resistant during treatment. A refractory cancer is also called resistant cancer.
The return of cancer after a period of improvement.
RNA is a biological molecule that occurs in virtually all living organisms, including some viruses. Chemically, it is very closely related to DNA. In fact, RNA is synthesized inside cells by copying DNA strands. Living cells use RNA especially as a messenger to convey genetic information so that our genes can make the proteins they need. RNA may also fulfill a number of other functions, taking part in many chemical reactions at the cellular level, for example.
In the CAR-T space, a suicide switch is a mechanism that will cause the CAR T-cell to kill itself to address a potential adverse event.
A T-cell, or T lymphocyte, is a type of white blood cell that helps trigger immune responses. T-cells find and destroy foreign pathogens such as bacteria and viruses, but they will also attack the body’s own cells if those cells have undergone abnormal (e.g. cancerous) transformations.
TALEN® is designed by fusing the DNA-cutting domain of a nuclease to TALE domains, which can be tailored to specifically recognize a unique DNA sequence. These fusion proteins serve as readily targetable “DNA scissors” for gene editing applications that enable us to perform targeted genome modifications such as sequence insertion, deletion, repair and replacement in living cells.
TALEN® is a registered trademark owned by the Cellectis Group.
The target site is the exact targeted location on a DNA sequence when willing to edit a genome.
TRAC or T-Cell Receptor Alpha Constant is a protein coding the gene TCR which is responsible for the T-cell recognition of foreign intruders in the body.
UCART (Universal Chimeric Antigen Receptor T-cells) are “off-the-shelf” allogeneic product candidates based on T-cells from healthy donors, whose production can be industrialized and thereby standardized with consistent pharmaceutical release criteria, over time and from batch to batch.
Vectorization consists of combining a vector with an active substance to adapt and control it towards a target and ensure its efficient delivery. Cellectis uses a virus to introduce certain traits into cells.