Engineered CAR T-Cell Therapy

The immune system has evolved to protect the body from invading pathogens or external harmful materials by identifying these foreign bodies through “non-self” antigens, which are molecular signatures that they carry and are foreign to the body. A central function of the immune system is to discriminate between “self,” which is recognized through antigens normally present in the body and borne by cells, proteins, sugars or lipids, and “non-self”, which is detected through abnormal or foreign antigens. Cancer cells thrive, in part, because they trick the immune system into treating them as self, even though they express abnormal antigens, and thus immune tolerance occurs when the immune system fails to recognize and attack tumors. Breaking immune tolerance is an important aspect of most immuno-oncology based therapeutics because it enables the immune system to recognize and treat tumors as nonself and lead to tumor destruction.

Cellectis’ therapeutics programs are focused on developing products 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. CARs are artificial molecules that, when present at the surface of immune effector cells, will enable them to recognize a desired protein, or antigen, and trigger the killing of cells harboring this antigen at their surface (target 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.

Leukemia

Leukemia is a cancer that originates in the blood stem cells (immature blood cells) which are found in the bone marrow. The blood stem cells can become either lymphoid stem cells or myeloid stem cells. Lymphoid stem cells turn into lymphocytes, a type of white blood cell. Lymphocytes are usually found in the blood and various parts of the lymphatic system, particularly in the lymphatic ganglia and the spleen. Lymphocytes manufacture antibodies, whose role is to fight infections.

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is an abnormal proliferation of lymphoid stem cells blocked at an early stage of differentiation. ALL develops rapidly, within a few days or a few weeks of the first symptoms. Acute lymphoblastic leukemia (ALL) accounts for approximately 20% of adult leukemias and more than one third of cancers in children.

Chronic lymphocytic leukemia

Chronic lymphoid leukemia (CLL) is a disease of the blood characterized by an excess of white blood cells in the blood and which develops slowly (chronic). In the case of chronic lymphoid leukemia, the B lymphocytes produced by the bone marrow accumulate in the blood, the ganglia, the spleen and the bone marrow, instead of dying within a few days or months to be replaced by others. It is the most common leukemia, affecting mainly people aged over 50.

Acute myeloid leukemia

Acute myeloid leukemia (AML) is due to the proliferation of blasts – cells that give rise to white blood cells that have become tumoral – in the bone marrow which can then no longer ensure the production of healthy blood cells. The frequency of acute myeloid leukemias (AMLs) increases after the age of 40, the average age being 65.

Multiple myeloma

Multiple myeloma, more commonly known as Kahler’s disease, is a disorder of the bone marrow caused by an uncontrolled proliferation of plasmocytes (blood cells of the family of white blood cells) specialized in the production of antibodies. In Kahler’s disease, the plasmocytes that proliferate all come from one abnormal plasmocyte. Multiple myeloma is a relatively rare cancer. This disease affects mainly people aged over 60.

T cell acute lymphoblastic leukemias

T cell acute lymphoblastic leukemias (T-ALLs) are aggressive hematologic tumors resulting from the malignant transformation of T cell progenitors.

Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and aggressive hematological malignancy derived from plasmacytoid dendritic cell precursors.

 

Solid tumors
Cancerous solid tumors, identifiable as a localized mass of cells, differ from cancers of the blood cells, such as leukemias, whose cancerous cells circulate in the blood or lymph and are dispersed into the body. The majority of cancers are solid tumors. Two types of solid tumor are differentiated:
• carcinomas arise from epithelial cells (skin, mucosa, glands).
• sarcomas, less common, arise from cells of the connective tissue (known as “supporting” tissue).

Pancreatic cancer

Pancreatic cancer is characterized by an anarchic proliferation of cells which forms a mass of tissue, i.e. a tumor, in the pancreas. Adenocarcinoma, which accounts for 95% of these tumors, is situated in the exocrine cells of the pancreas and is the most common type of pancreatic cancer. Although it is relatively rare, pancreatic cancer is one of the most formidable.

Non-small-cell lung cancer

Non-small cell lung cancer Non-small cell lung cancer (NSCLC) is an epithelial tumor of the lung. The most common forms of NSCLC are epidermoid carcinoma, large-cell carcinoma and adenocarcinoma, but there are other rarer forms. Non-small cell lung cancer (NSCLC) accounts for between 80 and 85% of lung cancers.

Glioblastoma

Multiform glioblastoma is a brain tumor which will affect the astrocytes, cells of the central nervous system. It is the most common brain cancer in adults and the most aggressive.