Personalised cancer vaccine, making progress against the disease

By Brice Prunas, gestor de Inteligencia Artificial en Oddo BHF AM

To this day, the most widely used and effective treatment for cancer (especially for solid tumors) is a form of immunotherapy called PD1 - also known as immune checkpoint inhibitor. The best-selling drug in this category is Keytruda from Merck US. While 75% of patients are cured after one year of this treatment, there is a possible risk of recurrence.

The personalized cancer vaccine (or PCV) should be seen as a booster aiming at meeting two objectives for cancer patients: a) to increase the cure rate (or pause in the progression of the disease) from 75% to a higher rate (beyond 80%); b) to allow the monitoring of the patient's immune system and to prevent a resurgence of their cancer.

Where are we in the development of this vaccine?

Moderna’s PCV is currently in Phase 2 of development and data should be released in the fourth quarter of 2022.

Merck US, the world leader in cancer treatment, which has had access to data from Moderna's open-label Phase 2 study, has decided to invest $250m in Moderna. The investment which aims to co-develop and co-commercialize the PCV gives a considerable positive signal about the vaccine's chances of success. The American oncology giant also has an economic interest in the success of Moderna's vaccine. Indeed, the success of the vaccine would enhance and extend the efficacy of its PD1 therapy which generates tens of billions in sales each year.

It is critical to understand that the Moderna study is being conducted in an "adjuvant setting" (i.e., only in cases where the tumor has already been surgically removed) which is a factor that greatly increases the chances of success of the Moderna study. The future will tell whether such a vaccine will be successful in a "metastatic setting" - this will be more difficult, but there is hope once we understand the essence of the messenger RNA method. Finally, this personalized vaccine should offer an even greater positive outcome in cases of melanoma compared to other solid tumor cancers.

How is the combination of Messenger RNA (MRNA) and artificial intelligence pushing the boundaries of science?

Until now, it was very difficult to identify tumor markers (i.e., proteins that are produced by the cancerous tissue itself or sometimes by the body in response to the progression of the cancer) because they were undetectable by the immune system. Therefore, the effectiveness of PD1 (a form of immunotherapy) hit its glass ceiling, making any progress in the fight against cancer quite complicated.

In response to this obstacle, Moderna's innovative approach is to:

1. Take a sample of each patient's tumor.
2. Sequence it.
3. Use elaborate algorithms to detect each patient's unique tumor mutation.
4. Then use Messenger RNA to label these mutant sequences (there are reportedly 34 in total)
5. Reintroduce the Messenger RNA into the cancerous tumor to generate this protein that will mark the tumor. In this way, the tumor markers become visible to the immune system and PD1 antibodies can more effectively kill the cancer cells. The benefits of this approach would be to get rid of tumors quickly and permanently, leading to a more permanent cure of patients.