What are CAR-T-cell cancer therapies?

Tuesday 31 January 2023, at 7 pm.

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What are CAR-T-cell cancer therapies?

Tuesday 31 January 2023, at 7 pm.
On-line debate.

  • In 2012, six-year-old Emily Whitehead was suffering from B-cell childhood acute lymphoblastic leukaemia and was in the Intensive Care Unit at the Children's Hospital of Pennsylvania. Her cancer had resisted conventional chemotherapy treatment and she was given no chance of survival. That is when Dr Carl June decided to administer her an experimental therapy he was researching into: CAR-T-cell anti-CD19 immunotherapy. Since then, Emily's leukaemia has been in remission for 10 years, and her case is a prime clinical example of how it is possible to turn the immune system into a powerful weapon against cancer.

    CAR-T, which stands for T-Cell Chimeric Antigen Receptor, is a type of therapy in which the patient becomes their own donor. It involves modifying the patient's T-lymphocytes to give them the capacity to attack cancer cells. T-lymphocytes, a type of white blood cell responsible for the immune response, particularly anti-viral and anti-tumour, are collected from patients by apheresis, a technique used to separate the components of blood. These lymphocytes are then genetically reprogrammed so that, when re-infused into the patient, they can recognise, attack and destroy cancer cells.

    CAR-T combines three types of therapy: cell therapy, immunotherapy and gene therapy. It is considered a cell therapy because a “living” drug is infused into the patient. It is an immunotherapy because the patient's own immune system cells fight the cancer cells. And, thirdly, it is a gene therapy (one of the first approved by the FDA) because the lymphocytes are genetically modified to fight the disease.

    The results obtained from using CAR-T-cell lymphocyte therapy are very promising and have been confirmed in blood tumours such as leukaemia or lymphomas, where it has shown to be effective mainly in people who have already exhausted other therapeutic options. More than ten thousand patients with blood tumours have been treated to date. This novel therapy is not, however, free from complications, such as certain toxicities or a decrease in the efficacy of the cells introduced into the patient. However, new CAR-T products are currently being designed to reduce these limitations, with work also focused on optimising treatments to reduce the incidence and severity of toxicities. The success of these early years has also driven a search for wider uses. In future, it is hoped that CAR-T-cell lymphocyte therapy can also be used as a potential treatment for other types of non-haematological cancer. In fact, the therapy is currently being tested in solid tumours such as glioblastoma, sarcoma, breast, ovarian, testicular and gastric cancer, and even in other diseases such as autoimmune pathologies and in transplant rejection.

    The challenges also include reducing the price of treatment. As with other novel therapies or drugs, price is one of the biggest obstacles to using the therapy. Most CAR-T treatments are supplied by a pharmaceutical company, and they are therefore the result of private clinical trials. This fact, together with other considerations (such as the high cost of acquiring knowledge from academic institutions), leads to very high treatment costs. However, in recent years various groups of haematologists and immunologists have set out to create so-called academic CAR-T cells. These are CAR-T cells developed at hospitals and, therefore, available at a more affordable cost. At present, both commercial and academic CAR-T clinical trials are being conducted in our country.

    Doctors Javier Briones and Manel Juan are pioneers in the development of CAR-T immunotherapies. Dr Briones’s group has led the creation of the first CAR-T in Europe for patients with classical Hodgkin’s lymphoma and T-cell non-Hodgkin’s lymphoma. According to the Spanish Society of Medical Oncology, Hodgkin’s lymphoma affects 3 in 100,000 people. Javier’s team has also developed new CAR-T 19 cells for patients with different types of B-cell non-Hodgkin’s lymphoma. Dr Manel Juan’s group has developed the first CAR-T in Europe for the treatment of acute lymphoblastic leukaemia, especially in adults, and other B-cell lymphoproliferative syndromes. More recently, moreover, his team has developed another therapy to treat multiple myeloma. Myeloma accounts for 10 % of bone marrow cancers and is the second most common blood cancer. Both initiatives are supported by ”la Caixa” Foundation.

    Speakers:

    • Doctor Javier Briones, head of the Clinical Haematology Unit and Director of the Cellular Immunotherapy and Gene Therapy Research Group at the Sant Pau Hospital Research Institute (IIB-Sant Pau).

    • Doctor Manel Juan, head of the Immunology Service at the Biomedical Diagnostic Centre (CDB) of the Hospital Clínic (HCB)-IDIBAPS, and of the Hospital Sant Joan de Déu and Hospital Clínic Advanced Therapies Platform.


    Moderadora:

    • Beatriz Pérez, journalist specialising in health for El Periódico de Catalunya.