Challenge 1: Prevention Vaccines

Vaccines already exist that prevent cancers caused by infection, such as against the human papilloma virus that causes some cervical cancers. But this challenge is to develop vaccines that work against non-viral cancers, which are caused by faults in our DNA that accumulate over time.

That’s what really makes this a Grand Challenge. Because cancer is a disease of the body’s own cells, it is more challenging to coax the immune system to recognize and eliminate early stage cancers, where the difference between healthy cells and abnormal cells might be very small.

But the promise is huge: imagine if we could vaccinate against cancer as we do for infectious diseases such as TB and measles. Grand Challenge could make this a reality.

Although the idea of vaccines to prevent cancer is not new, it is now closer to the realm of possibility thanks to recent advances in treating cancer using immune-based approaches.

The results of these treatments have clearly demonstrated that the immune system can recognise tumour antigens and generate impressive clinical responses. Current approaches include immune checkpoint blockade, adoptive T cell therapies, chimeric antigen receptor-expressing T cells and therapeutic vaccines, among others.

The success so far in demonstrating effective immune responses to cancer in the treatment setting provides the impetus to consider developing preventive vaccines for one or multiple forms of the disease.

These vaccines would be designed to stimulate the production of memory cells that could subsequently recognize and eliminate early-stage cancers or pre-neoplastic lesions when they appear.

There are a number of fundamental gaps in our knowledge of tumour immunology that could be filled by a team working on this challenge, such as whether the immune response to cancer is limited to neo-antigens (antigens expressed on cancer cells as a result of cancer-specific mutations) or mis-expressed self-antigens (antigens that exist on normal cells, but are altered or present in higher amounts on tumour cells.)

We are also yet to understand when and how the immune response is triggered by the presence of cancer cells, how the immune system sees them, why common mutational changes in cancer are not normally recognised by the immune system and whether immune responses can be stimulated against these.

Finally, there is the key question of whether the immune system’s tolerance of self-antigens can be broken without inducing autoimmunity.

This Grand Challenge relates to the prevention of cancer using a vaccine in healthy individuals, as opposed to therapeutic vaccination (in which the patient has already been diagnosed with cancer). It is also directed at cancers that are not caused by viruses such as HPV, HBV or EBV.

By addressing this ambitious challenge, we hope that the successful team will significantly advance our understanding in a number of key areas of cancer immunology, including determining the optimal combination of antigens and immune responses that would be most effective in the context of a vaccine to be used broadly for the prevention of one or multiple types of cancer.

This will require specialist input in immunology and inflammation from scientists not normally working on cancer in addition to those with an understanding of tumour immunology specifically.

Teams taking on this challenge will need to describe their strategies to test the effectiveness of vaccines in people as well as in animal models of cancer.  It will also be critical to address the difficulty of producing a preventive vaccine for cancer without inducing unacceptable auto-immune responses.