Analysis: Adoptive immune cell therapy is a 'living drug' that uses live immune cells to target and kill cancer cells
What is adoptive immune cell therapy?
Autologous vs Allogenic
Immune cells used for adoptive immune cell therapy, originate from the patients themselves (autologous) or from someone other than the patient (allogenic). These immune cells must have a receptor on their surface to recognise a unique protein on a cancer cell, and machinery inside them to kill a cancer cell. They are collected from the blood of the patient with cancer or a healthy donor, or from the tumour of the patient with cancer. They are grown in a sterile laboratory to generate greater numbers of the same cell and returned to the patient after lymphodepleting chemotherapy.
Engineered vs non-engineered
Immune cells used for adoptive cell therapy can be either engineered or non-engineered. Not all immune cells with the machinery to kill cancer cells have the receptors to recognise cancer cells. Immune cells can be engineered in the laboratory to provide them with a Chimeric Antigen Receptor (CAR) or a T Cell Receptor (TCR) enabling them to recognise cancer cells. Non-engineered immune cells taken from the tumour, known as Tumour Infiltrating Immune Cells (TILs), are more likely to naturally recognise cancer cells in a solid tumour than immune cells from blood.
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From RTÉ Radio 1's Drivetime, The Irish Cancer Society on why we need more clinical trials in Ireland
Blood vs solid cancers
As of June 2024, there are six CAR T-cell products approved to treat blood cancers in the European Union. Patients with blood cancers, which had dismal outcomes from standard treatments, are now achieving much higher response rates from CAR-T Cell Therapy. Since 2021 patients with blood cancers have been treated with CAR T-cell therapy in St. James’ hospital in Dublin. CAR T-cell therapy may not work for every patient and ongoing research aims to improve patient responses.
Initially the CAR-T cells that were developed for blood cancers struggled to treat solid cancers. They couldn’t get from the patient’s blood to the tumour in enough numbers and once there couldn’t survive long enough in the toxic tumour to kill it.
Researchers have investigated several solutions in recent years, two of which have made it to the clinic in the United States. In February 2024 the Food and Drug Administration (FDA) granted approval for an adoptive cell therapy (lifileucel) to treat advanced melanoma with non-engineered tumour-infiltrating lymphocytes (TILs). In August 2024 the FDA approved a T-cell receptor (TCR) engineered adoptive cell therapy (afami-cel), to treat people with metastatic synovial sarcoma. At the time of writing, these therapies have not been approved by the European Medicines Authority (EMA).
From the US National Cancer Institute, what is T-Cell Transfer Therapy?
What advances are in the pipeline?
Reduce treatment costs
By far the greatest limitation is the cost to manufacture adoptive cell therapies. In Ireland and most of Europe it costs over €300,000 per patient for commercial CAR T-cells. Whereas a hospital in Spain makes their own at one-third the cost of commercial CAR T-cells.
Reduce time to make an adoptive cell therapy
A smaller number of high-quality CAR T-cells are superior to a higher number of poor-quality CAR T-cells. It typically takes nine to 14 days to grow CAR T-cells and if a patient has an aggressive cancer, it is also growing rapidly during this time. Researchers have developed methods to grow enough high-quality CAR T-cells within 24 hours to three days by simplifying the manufacturing process. Instead of expecting CAR T-cells to grow to greater numbers in a dish in the laboratory they let them do this in the body.
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From RTÉ Radio 1's Today with Claire Byrne, TCD Professor Luke O'Neill on how thousands of cancer patients in England are to trial personalised vaccines
Vaccine-like mRNA injections to engineer CAR T-cells in the body
Immune cells are engineered in the laboratory to permanently have a Chimeric Antigen Receptor which gets passed to their daughter cells, living on in the patient for months to years. In some patients it can result in the loss of antibody producing cells, making patients more susceptible to infections, a major cause of death in CAR T-cell recipients that were cancer free.
Researchers are now trying out the same mRNA technology used in the COVID-19 vaccine to add a temporary CAR to immune cells. The CAR will only be present on immune cells while the vaccine-like mRNA injection is being given to the patient. This is an in vivo CAR-T therapy, whereby the CAR T-cells are produced in the body, not in the laboratory, and the side effects are temporary.
Combining cancer surgery and adoptive cell therapy
The size and toxic environment of solid tumours can be overwhelming to adoptive immune cells, if they manage to make it to the tumour. There are clinical trials assessing the combination of adoptive cell therapy with surgery for types cancers where tumours are difficult to remove completely by surgery, such as brain cancer. The idea is that immune cells, put into the site where the tumour has been removed, will eliminate cancer cells left behind after surgery and prevent the cancer growing back or metastasising.
What do patients need, where and when do they need it?
A faster, simpler, cheaper and more equitable immune cell therapy to treat more patients with blood and solid cancers, accessible in at least one hospital in each province in Ireland now.
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The views expressed here are those of the author and do not represent or reflect the views of RTÉ
