There has been gradual progress in our understanding of immune regulatory mechanisms, thanks to the discovery of a diverse range of immune cells — from anti-inflammatory “brakes” on the system to pro-inflammatory “accelerators”. The goal for all immune modulation, whether boosting anti-inflammatory or pro-inflammatory cells, CAR-T (the modification of immune cells to target cancer cells) or other manipulation, is re-establishing and supporting the body’s natural homeostasis.

Future Horizons:

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5-yearhorizon

The roots of autoimmune disorders are understood

Clinical trials build evidence that cancer vaccines induce an immune response that prevents cancer from returning after tumour-removing surgery. Reduced immune toxicity makes CAR-T therapy safer and more accessible for patients of all ages. Results of lupus immunotherapy trials deliver new insights into mechanisms by which immunotherapy is resetting the immune system

10-yearhorizon

Immunomodulation becomes supercharged

Synthetic biology approaches are developed to deprogram the immune system. Microfluidic devices, models used to recapitulate tumour complexity, start to decipher the molecular mechanisms driving treatment inefficiencies and to evaluate new targeted immunotherapies. New treatments are developed for a rare disease of the white blood cells that control the immune system and guard against repeat infections and cancer; insights from this development inform new research into the broader immune system.²¹ AI starts to make links between personal history and autoimmune disorder development.

25-yearhorizon

Immune hacking gets local

Therapeutic approaches scout immunity locally instead of making systemic changes: localised rewiring, with RNA, and local delivery tools like nanoparticles. This ends systemic side effects. A better understanding of the immune system leads to precise gene editing of immune cells, making it possible to identify errors in specific types of cells and optimise or personalise treatment for better function of the immune system. A one-time cure for HIV — that does not require being on lifetime medication – is developed using CAR-T cells to purge the viral reservoir.²² A better understanding of immune system behaviour enables development of one global vaccine for cancer.

Immunotherapy (adding specifically curated receptors to the T-cells of the immune system and others to recognise cancers and other desired targets, commonly referred to as CAR-T cell therapy) has delivered on its early promise against cancer. But it remains more effective for cancers like leukaemia, lymphoma and melanoma than for inaccessible and immunosuppressive solid tumours. Even for non-solid cancers, CAR-T can fail or induce cytokine toxicity. Lentiviral vectors, derived from the HIV-1 retrovirus, are showing promise to deliver gene editors to tumours and against other immune disorders.¹³, ¹⁴ Trials are also now beginning in England¹⁵ and the US for cancer vaccines that work by stimulating a patient’s immune system to recognise and destroy any remaining cancer cells — and stop their reappearance.¹⁶

Immunotherapy is not just being investigated for cancer. For people with gene errors predisposing them to immune dysfunction, gene-editing techniques show promise to precisely correct T cells wrongly targeting the body’s own healthy cells. CAR techniques being used against multiple sclerosis¹⁷ as well as myasthenia gravis,¹⁸ stiff-person syndrome¹⁹ and even intractable lupus²⁰ are showing promising early results, along with strategies against other autoimmune disorders.

However, all this is fighting symptoms. A future medical approach to address the underlying cause of immune-system dysregulation will require a more precise understanding of the triggers for autoimmune disease.

Hacking immunity - Anticipation Scores

The Anticipation Potential of a research field is determined by the capacity for impactful action in the present, considering possible future transformative breakthroughs in a field over a 25-year outlook. A field with a high Anticipation Potential, therefore, combines the potential range of future transformative possibilities engendered by a research area with a wide field of opportunities for action in the present. We asked researchers in the field to anticipate:

The uncertainty related to future science breakthroughs in the field
The transformative effect anticipated breakthroughs may have on research and society
The scope for action in the present in relation to anticipated breakthroughs.

This chart represents a summary of their responses to each of these elements, which when combined, provide the Anticipation Potential for the topic. See methodology for more information.