Can we make a new cancer therapy with on-target efficacy and minimal side effects?

Professor Simon Barry talking with Lee Hutton on cancer immunotherapy …

In our last conversation, we discovered how the new treatment (“immunotherapy”) is “an umbrella term that captures the way which the body harnesses the immune system and makes it better at recognising cancer cells in the body”.

In brief, it was explained that clinics have been recently able to treat patients with certain cancers using “antibody immunotherapy” with success. In the last 12-14 months the new CAR T-cell immunotherapy for some blood cancers has been approved for use. It is enlightening to understand how cancer cells “communicate” with the immune system cells and even see the electron microscopy pictures of the immune system cell sending out “fingers” to “taste and sniff”. This is their way to check out the cancer cell. We learnt how the cancer cells send back “leave me alone” messages and this can leave the body vulnerable to non-detection of the cancer.

The new wave of immunotherapy called CAR T-cell therapy has the promise of arming the immune system so as to be resistant to the “hypnotising effect” of cancer cells upon the immune system cells. CAR T-cells are armed with a “key” that recognises the cancer cell “lock”, and when they meet, this enables the CAR T-cell to kill the cancer cell.

If we can find the right “key”, CAR-T therapy also has the potential to be effective against a larger range of solid cancer tumour types. Prof. Simon Barry’s laboratory and his cooperative research team are continuing to develop this scientific breakthrough. Whereas antibody therapies target “check point inhibitors” to block the hypnotising messages being sent from the cancer cells, CAR-T therapy aims to give the immune system cell a “licence to kill” upon instant recognition of a cancer cell. In discussing CAR-T therapy and how it works, Prof. Barry used the analogy of the “lock and key”. CAR-T therapy depends on arming the immune system T cells with a “key” with which to recognise the right “door” – i.e the cancer cell. The discovery of the “key” for leukemia cancer cells of a protein CD 19 is an example. So far this key is effective only against this particular subset of cancers.

Q: What is the UPDATE from the lab since our last publication?

A: We are still very excited about a “key” that has proven to be effective in lab conditions against nine types of cancers that include: triple negative breast; prostate; pancreas; ovary; glioma; and neuroblastoma (two very difficult to treat brain cancers). We have some promising data using mouse models for two of these, but we need to repeat those experiments carefully to make sure the results are reproducible. However, since then we have now ADDED to this list: lung cancer; lymphoma; colorectal cancer; myeloma; head and neck squamous cell carcinoma. It is also very cool that the lab’s CAR T-cell “key” has been used successfully to kill ovarian cancer cells using a patient biopsy sample rather than a cell line in the lab or a mouse model … so that represents further promise. That makes it a total of 13 different cancer family types.

Q: What is the lab focussing on now?

A: As well as testing which cancer type we can target, we are working on how to make the CAR-T up to the number and quality for clinical use. There are quite a few things we want to get right:

1. “Best Formulation” – that is figuring out and growing the right mixture of cells to be put into a person to mimic the immune system cell armoury and what “cocktails” to grow the cells in, such as different mixtures of hormones. This is very clinically important to its effectiveness and we understand that the immune system operates in waves so it needs to be armed with CAR T-cells that are in varying stages of readiness to kill cancer cells. So a patient will be delivered some cells “ready to go and find and kill”, and some cells capable of doing the same but waiting to be activated, and some cells that are capable but having a rest until “called back into service”.
2. To make the CAR T-cells most effective once in a person, they need to be able to find the cancer cell (“door”) in the complex environment of the human body. To use the key and door analogy, the body may be analogous to a big city of dark streets lined with thousands of doors, and the CAR-T immune cell must be able to find the right door (cancer cell). We are working on programming the CAR T-cell with the sensitivity to discover the signals that cancer cells use to draw other cells to it. This is called “homing” to a tumour.
3. Getting “GMP” (Good Manufacturing Process) ready … i.e. making sure the manufacture of the cells is very safe and clean to put into a person, then we can proceed to set up our trial plans.

Q: BUT, what does it take to get this science from the lab, to curing people in clinical trials?

A: Great Question! There are two pathways and we are doing both:

1. Through research funding (clinical trial grants) for which there is fierce competition amongst researchers from all fields.
2. Create a company with other organisations, enabling access to federal programs and also partnering with investors as a joint venture – I am part of a team that is a big collaboration of Women’s and Children’s Hospital; University of SA; and Adelaide University. Together we have formed a Biotech company called “Carina Biotech”. You can read more about the research team/partnerships and progress of Carina Biotech at our website https://carinabiotech.com/ (apart from the play on words related to “CAR In a Biotech”, an extra bit of trivia is that the name was chosen because of its link to a constellation called Carina, which represents the ship featuring in the greek mythology “Jason and the Argonauts”, and their search for the golden fleece!).

Q: How is your timeline estimation of having trials by the end of 2020 going?

A: Given the process of gaining approvals from an ethics and safety point of view is usually a 12-24 month runway, we are being extremely ambitious! However, we are also working on another aspect of the nuts and bolts of reaching clinical trial readiness, which concerns the costs of the method used to deliver CAR T-cells to the immune system of a person. The method uses a “trojan horse virus” which is then removed before the cells are delivered, and that currently costs hundreds of thousands of dollars. So, as a bigger picture thing we are also looking at ways we can partner with other organisations to set up infrastructure in South Australia (a manufacturing facility) so we can deliver the therapy here: “Home grown in SA”.

Thank you Prof. Barry again for this update and we look forward to your presentation in February next year, so our Cancer Care Centre members and nearby residents of Unley can meet you and understand more fully these important immunotherapy breakthroughs in cancer treatments.

[You can also read part one of Lee Hutton’s interview with Prof. Simon Barry about cancer immunotherapy in the July-September 2019 Healthy Living magazine.]