A promising new vaccine against melanoma

26 Sep 2018 Samuel Vennin

Senior author Bruce Beutler from the University of Texas Southwestern Medical Center.

Researchers from the University of Texas and the Scripps Research Institute have demonstrated that adding a new adjuvant, Diprovocim, to a cancer vaccine can draw cancer-fighting cells to the tumour site and boost the immune response (PNAS10.1073/pnas.1809232115).

As cancer spreads, it inhibits the activity of T cells, the immune cells responsible for fighting off cancerous cells. Immunotherapy aims to harness the immune system to combat tumours and lately, cancer vaccines have been investigated as a potential trigger for this reaction. The vaccines are usually associated with adjuvants, molecules that are added to enhance the immune response to some specific antigens. This addition usually augments the response to cancer antigens both inside and outside of the tumour, making the vaccine more efficient.Senior author Dale Boger.

Several adjuvants have been reported to improve the immune response in preclinical models for cancer treatment, but they are difficult to synthesize and can be toxic as they disseminate within the host organism. To find a safer alternative that would be easier to produce, a research team led by Bruce Beutlerand Dale Boger screened a library of synthetic compounds. The researchers identified an adjuvant, Diprovocim, that is able to bind to the same immune receptors (TLR1/TLR2) as other adjuvants commonly used, while bearing no structural similarities and hence reducing the aforementioned shortcomings.

100% success in mice

The researchers tested this adjuvant on mice with a common form of aggressive melanoma. All mice in the experiment were given the anti-cancer therapy anti-PD-L1. They were then split into three groups: eight received the cancer vaccine, eight received the cancer vaccine plus Diprovocim, and eight received the cancer vaccine plus an alternative adjuvant derived from aluminium, alum.

The results spoke for themselves. All mice who received the cancer vaccine/Diprovocim combination were alive after 54 days, while none of the mice who were only given the vaccine (without Diprovocim) survived longer than 38 days. Comparatively, only 25% of the mice treated with the cancer vaccine with alum survived past 54 days.

Further investigations showed that Diprovocim boosted the ability of the vaccine to fight tumours by stimulating the immune system to produce more T cells, a feat that the other two vaccines could not achieve. Those T cells contributed to eliminating about 70% of target cells in mice immunized with the vaccine containing Diprovocim, compared with about 10% in mice who received alum as an adjuvant.

Preventing tumour recurrence

The vaccine is not just effective at suppressing tumours, it can also prevent them from reappearing. When the researchers tried to re-establish tumours in the surviving mice (without giving them any further treatment), the tumours failed to expand in mice treated with Diprovocim, while they grew rapidly in those who received alum. This finding shows that Diprovocim produces antigen-specific responses that protect the mice from tumour regrowth.READ MORE

Cancer ‘vaccine’ eliminates tumours in mice

One important feature of this technique compared with others lies in the site of injection. Unlike some vaccines being developed, this Diprovocim-based alternative does not need to be injected directly into the tumour. Here, the researchers gave it as an intramuscular injection away from the tumour site.

This new vaccine obviously requires further testing and trials on other types of tumours and in combination with different cancer therapies, but these promising results provide grounds for optimism in the quest for an efficient cancer treatment.

Samuel Vennin is a PhD student contributor to Physics World. Samuel is studying cardiovascular medicine and numerical modelling at King’s College London. Find out more about our student contributor networks

26/9/2018     from physicsworld.com