Tissue Study in Patients Undergoing CAR-T Cell Therapy

The "CAR-T" immunotherapy ("Chimeric Antigen Receptor T cell therapies") is a therapy based on T cells expressing a chemical receptor for a specific antigen indicated for patients with some types of oncohematological pathologies that have not responded to other forms treatment, such as: relapsed or refractory non-Hodgkin's lymphomas, including diffuse large B-cell lymphoma, primary B-cell mediastinal lymphoma, transformed follicular lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, in children and young adults (<26 years) and multiple myeloma. This therapy is an absolutely innovative approach which consists of a personalized live cell immunotherapy that modifies the recipient patient's immune system to make it able to recognize and eradicate the neoplastic cells expressing the antigen towards which the cells have been engineered. CAR-T therapy uses specific immune cells (T lymphocytes) of the patient, isolated from his peripheral blood, engineered through the integration of genetic material encoding the chimeric receptor, expanded in vitro and then re-infused to activate the immune system response against the disease.

This approach has several biological advantages:

1. to supply the patient with "reprogrammed T cells" with a new and specific activation mechanism;
2. overcoming immune tolerance towards cancer cells;
3. bypassing HLA-mediated antigen recognition restriction mechanisms; The CAR-T therapies that have obtained the Marketing Authorization (AIC) in the European Union and in Italy are: the drug Kymriah, drug Yescarta.

The therapeutic indications for which they have been approved are:

• Kymriah (tisagenlecleucel): pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia who have never responded to chemotherapy, or who have relapsed after allogeneic haematopoietic stem cell transplantation or after at least 2 lines chemotherapy; patients with diffuse large B cell lymphoma or DLBCL who have already undergone at least 2 lines of systemic therapy;
• Yescarta (axicabtagene ciloleucel): patients with diffuse large B cell lymphoma or DLBCL, primary mediastinal B cell lymphoma or PMBCL who have already received at least 2 lines of systemic therapy. CAR-T therapies represent an important therapeutic option for the lymphoproliferative diseases listed above and have been studied in patients in whom previous standard strategies (chemotherapy and haematopoietic stem cell transplantation) have not proved effective.