PCaSO AGM 25 July 2022 (via Zoom).

Notes from talk by Professor Edd James, University of Southampton.

Professor James’ career has been focussed on the human immune system, particularly in understanding and exploiting immune responses in the battle against cancer.

Tonight’s talk was accompanied by a number of Powerpoint slides.

The Southampton University Cancer Centre was built some 4 years ago and is the first dedicated immune research site in the UK. The Centre investigates why cells become cancerous, what causes faults in the DNA ‘instruction manual’, and the impact of environmental, natural, inherited and viral influences. These all represent the ‘Hallmarks of Cancer’ and associated risk factors.

Most cancers invoke mechanisms that avoid or deceive the immune system and can hence grow without restriction.

Current treatments for all types of cancers can involve surgery, radiotherapy, chemotherapy, hormone and immunotherapy. The latter has already been shown to leave patients cancer-free after 5 years or so.

The immune system has the ability to identify and kill cancer cells, including pre-cancerous cells in patients who have no actual symptoms (asymptomatic). The body’s main natural weapon is the ‘Killer T’ cells, derived from lymph glands and spleen. Each Killer T cell can locate and destroy a number of cancerous cells, one by one. We need more understanding of how this works!

Cancer cells have mechanisms to hide or disguise themselves from the T cells, or even switch off the immune response. If the T cell doesn’t recognise a cell as clearly cancerous, it will leave that cell alone, as the T cells cleverly avoid ‘friendly fire’ ie accidentally destroying normal cells.

The ways in which immunotherapy combats cancer are 1) antibody therapy, by injecting the patient with cancer-targeting cells, 2) vaccination to improve the immune response, and 3) Checkpoint Inhibition that ‘releases the brakes’ on Killer T cells. The vaccination process takes the patient’s own cells and feeds them with prostatic acid phosphate, after which they are injected back into the patient. This has been trialled to attack the active cancers in patients with advanced disease.

In the last few years, knowledge has increased on proteins and antigens to show what the cancer cells are ‘displaying’, and to steer the T cells to them accordingly. Chimeric Antigen Receptor (CAR) T cell therapy engineers the T cells to recognise specific antigens. Early trials on resistant or advanced cancers have been encouraging.

Further research has examined combinations of immunotherapy pathways that stimulate the immune response whilst also reducing the patient’s chemotherapy needs. Further research will highlight the categories of patient for whom this could work best.

There is a significant number of immunotherapy trials already underway. If only 10% of these are found two be effective it will represent major progress in the war against cancers, with better therapies, lower side effects, a personalised approach and increased healthy survival rates.

Notes from questions raised after the talk:

• • Immunotherapy can have a role in developing hormonal Androgen Deprivation Therapy (ADT), as a front-line treatment, but with reduced side effects.
  • There is a treatment in the USA called ‘Provenge’ but it costs £90k and is not approved in the UK excepting for certain rare cases.
  • A brief video-microscope film was shown of T cells attacking cancerous cells.
  • Although some lymph glands are removed as part of prostatectomy surgery, other lymph glands around the body remain active, producing T cells.
  • Other leading centres of cancer research include Royal Marsden Hospital. There is increasing recognition of the need for developing networks and pooling resources.
  • Practising clinicians are generally very receptive to the research, although better communications would help, notably in Oncology. Medical journals are used, and specialist conferences, although the latter were paused due to Covid.
  • It was noted that if patient recruits are needed for new trials, PCaSO could reach out to its members and on the website.