Multiple myeloma is the clinical name for bone marrow cancer. A disease that often attacks those in their 60s and 70s, it can be slowed but not cured. It is the second largest blood-based cancer after lymphoma.
Adaptimmune, based at Milton Park, has been researching the use of modified T cells for more than ten years. T cells are part of the body’s immune system and will recognise and attack abnormal or rogue cells.
An early phase clinical trial in the United States has shown positive results against myeloma, using the patients’ own T cells — genetically modified to attack the cancer cells.
Once diagnosed, the standard initial treatment is chemotherapy, followed by a bone marrow transplant. The transplant’s aim is to ‘wipe the slate clean’ of the infected marrow and is known as an autologous stem cell transplant or SCT.
Adaptimmune’s trial is to add the patient’s engineered T cells to the SCT. These T cells carry receptors that help them recognise and attack a tumour, while ignoring healthy tissue.
In common with most cancers, myeloma comes in varying types and has various stages. An early pre-cancer stage is called smouldering, where there are abnormal cells but no symptoms.
Chief operating officer Dr Helen Taylor-Martin said: “That is what we term the watch and wait stage.”
One warning sign of myeloma is an unexplained bone fracture. Another is a huge spike in the levels of a certain protein.
The protein results from antibodies that take over the bone marrow space and it attacks the kidneys. Renal function is significantly affected and the problem can lead to renal failure.
Part of the US trial measures the drop in the protein’s level as an indication or marker of the efficacy of the T cells against the tumour.
From its early days, Adaptimmune has worked closely with the University of Pennsylvania, one of very few centres which has the staff, knowledge, premises and equipment to engineer T cells to the required regulatory standards.
Pennsylvania’s university is well-placed to conduct the trials, having conducted some 25 such tests using similar technology.
The US medical system differs from the UK and lends itself to these kind of trials. While UK care is geographically based, the US has disease centres and these attract patients from all over the country.
Such centres can see as many as 1,000 patients a year, a significant number in clinical trial terms. In addition to the myeloma trial, Adaptimmune has also conducted studies on other cancers in collaboration with the university.
This first myeloma trial targeted six patients; the second phase extended to a target enrolment of 26 patients. To date, 15 patients have been enrolled and of these, 13 have been assessed at day 100 and 11 have reached a minimum of six month follow up of the tumours’ response to treatment.
In 2013, Adaptimmune will establish identical trials in Europe, which means finding the right centres and partners that can offer the same kind of facilities and expertise as the University of Pennsylvania.
Two UK sites are included in the shortlist. Trials will be extended beyond myeloma to melanoma, sarcoma and oesophageal cancer.
Sarcomas are rare cancers that develop in the supporting or connective tissues of the body such as muscle, bone, nerves, cartilage, blood vessels and fat.
For myeloma, trials of just the engineered T cells without an SCT will be conducted. The reasons are twofold. One is that using the T cells with an SCT can make it harder to gauge which has produced the better response, the T cells or the SCT.
Second is that patients are often ineligible for an SCT, or the one they have been given has failed.
Ineligibility frequently arises from physical condition — the after-effects of the initial chemotherapy or the patient’s general condition, especially if elderly.
Current drugs have extended life expectancy for myeloma sufferers from the original one to two years up to three to five years, but a complete cure is rare.
The Adaptimmune therapy is following the growing trend for personalised medicines. We all vary genetically and a one size fits all approach may benefit some but not others.
Tissue typing is a key element in the process, with patients that will most benefit being selected.
Adaptimmune and sister company Immunocore trace their roots back to Avidex, founded in 1999 as a spin-out from Oxford University to develop and commercialise novel T cell receptor (TCR) technology invented by Dr Bent Jakobsen. He is now chief scientific officer of both companies.
Adaptimmune was founded in Pennsylvania in 2011 to help manage the clinical programmes.
Funding comes from a private source, not standard venture capital backing.
Dr Taylor-Martin said: “Taking Bent Jakobsen’s initial studies to this point has been quite a long road but we are now seeing the fruits of our labours. We look forward to our T cell platform underpinning treatments for a variety of cancers and diseases.”
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