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Evolution of cancer immunotherapy: from bone marrow transplant to CAR

The latest advance in the field of immune therapies against cancer are the active and targeted CAR therapies. This treatment consists of obtaining the patient's lymphocytes and reprogramming them to attack the malignant cells. CAR therapies are, until now, the most sophisticated, since they are "active" treatments that use living cells that proliferate, and at the same time, are directed against a specific target.

They are known as CAR therapy because the reprogramming of the patient's immune cells includes the incorporation of a "Chimeric Antigen Receptor" (CAR). Once reprogrammed in the laboratory, these lymphocytes are able to manufacture and express this receptor in their membrane, which makes them change their function and begin to eliminate the tumor cells.

Although immunotherapy is already an essential therapy of cancer treatment, through innovative and increasingly complex therapies, we must not forget that immunotherapy-based treatments have existed since the 70s.

The Hospital Clínic was a pioneer in this field and became the first hospital in Spain to do a bone marrow transplant. This procedure constitutes the first immunotherapy modality because it uses the donor's immune cells to eliminate the patient's tumor, which is known as the "graft-versus-tumor effect". This therapy nowadays is still a fundamental treatment against cancer.

After the bone marrow transplant, other immunotherapy treatments appeared, called "passive" immunotherapy, which uses monoclonal antibodies and not living cells. The first to develop were anti-HER2 monoclonal antibodies for an important subgroup of patients with breast cancer HER2 +.

Finally, in the last few years active immune therapies, such as CAR therapies, have appeared. To date, the most developed CARs in the clinic are those whose target is CD19, a protein found in most of the tumor cells of patients with non-Hodgkin's lymphoma, chronic lymphocytic leukemia and acute lymphoblastic leukemia.

From the Hospital Clínic an intense work has been done in these new treatment modalities. Thus, the "Immunotherapy Section" has been created within the Immunology Service, led by Dr. Manel Juan, who is responsible for CAR therapy and similar therapies. In the area of research, the first phase 2 assay was coordinated with ARI-0001 cells. In addition, although this trial is carried out in 10 centers in Spain, all cell production is done from the Hospital Clínic.

On the other hand, tha Hospital has collaborated with different industries and institutions, such as the Banc de Sang i Teixits, pharmaceutical industries and regulatory agencies, with the aim of achieving the application of these treatments as quickly as possible.

In this regard, the European Medicines Agency approved in June 2018 two commercial anti-CD19 CARs therapies, which are only administered in appropriately certified centers, among which the Hospital Clínic has made an effort to set up to be one of the chosen centers.

Currently, CAR therapies have been developed against the CD19 antigen only for hematological tumors. This tumor marker is present in all cancer cells, but in the case of hematological cancers, malignant cells are found in blood, which is easier to access. At the moment, the way to facilitate the access of the CAR lymphocytes to tumor cells in other parts of the body has not been found, this is the current goal of many researchers from different countries, who are working to apply these same therapies in solid tumors.