Collaborations in Cancer and HIV Cure Research

The HIV Cure & Cancer Forum brought cancer and HIV researchers together in Paris, as a prelude to the International AIDS Society Conference on HIV Science. The forum explored overlaps between the two fields and the advantages of establishing collaborations.

What do HIV and cancer have in common? What can HIV researchers gain by looking to the cancer field for inspiration? For starters, treating cancer led to the only HIV cure to date. Timothy Ray Brown was HIV positive and had leukaemia. He received a stem cell transplant which was cleverly selected to be resistant to HIV, and Timothy is now into his eleventh HIV-free year.

Notable HIV researchers Françoise Barré-Sinoussi, Steve Deeks and Sharon Lewin wrote a blog post addressing the types of research that could benefit from a collaborative approach. Many avenues of investigation in both fields have common ground.

The HIV Cure and Cancer Forum addressed issues including:

Measuring the burden of disease 

Both HIV and cancer researchers need to be able to understand the extent of disease. How many diseased cells are there? Where are they? Research in this area addresses the tricky question of how to distinguish healthy and diseased cells. It is not easy to tell cancer cells or cells with latent HIV apart from normal cells. Often they are found in parts of the body that are difficult to access.

Understanding disease persistence

Gene expression is controlled by a complex set of mechanisms known as epigenetics. Epigenetic changes typically involve DNA modifications that change its shape and behaviour. These changes affect how easily genes are expressed. Epigenetic changes influence both HIV latency and cancer. Understanding epigenetics can shed light on the mechanisms of disease. It can also lead to the identification of targets for intervention. Drugs that modify epigenetic changes are available, including vorinostat and romidepsin. These drugs can alter gene expression, and are mostly licensed for treating cancers. Epigenetic modifying drugs could form part of a ‘kick and kill’ or ‘tickle and tease’ strategy to chase latent virus out of hiding before eliminating it.

Improving knowledge of immune evasion

HIV and cancer have ways of dodging the immune responses that could clear them. Both cause chronic inflammation which suppresses the host immune response. They both also alter the expression of immune checkpoint markers. These markers are essentially ‘off switches’ for beneficial immune responses. Immune checkpoint blockers (including anti-PD-1), are used to treat certain cancers. They have enormous potential to treat HIV. HIV researchers have an opportunity to benefit from the work done by oncologists to set up treatment regimens that minimise side effects.

Strengthening immune responses

Developing strategies to boost beneficial immune responses is the extension of grasping how HIV and cancer turn them off . Vaccine strategies could enhance immunity. Immune modulators such as cytokines or modified regulatory T cells could also boost immunity.

Developing gene therapy strategies 

Editing host genes to better respond to or block HIV would be an incredibly powerful tool. Strategies for treating cancer, including chimeric antigen receptor (CAR) T cells, are now being adapted to treat HIV. Other gene editing strategies, such as CRISPR-Cas9, could fundamentally change disease susceptibility.

Learning from each other

Years of collaboration between basic scientists, clinicians and community members provide a strong model for research. Partnerships have shaped HIV research, and are powerful for conducting robust studies that participants support. Strategies and technology from the cancer field can inform HIV research, and cancer researchers can gain from the partnership approach that has been pioneered in the HIV field.

Other resources on the HIV and cancer overlap

Carl June’s talk at CROI in February 2017 – linked here

Immune checkpoints in cancer and infectious disease

Lessons from cancer for PD-1/PD-L1 therapy in infectious diseases

T cell engineering in cancer and HIV

Cancer immunotherapy and influence on HIV cure

International AIDS Society press release about the Cure and Cancer forum – here