Abstract
In situ cancer vaccination refers to any approach that exploits tumour antigens available at a tumour site to induce tumour-specific adaptive immune responses. These approaches hold great promise for the treatment of many solid tumours, with numerous candidate drugs under preclinical or clinical evaluation and several products already approved. However, there are challenges in the development of effective in situ cancer vaccines. For example, inadequate release of tumour antigens from tumour cells limits antigen uptake by immune cells; insufficient antigen processing by antigen-presenting cells restricts the generation of antigen-specific T cell responses; and the suppressive immune microenvironment of the tumour leads to exhaustion and death of effector cells. Rationally designed delivery technologies such as lipid nanoparticles, hydrogels, scaffolds and polymeric nanoparticles are uniquely suited to overcome these challenges through the targeted delivery of therapeutics to tumour cells, immune cells or the extracellular matrix. Here, we discuss delivery technologies that have the potential to reduce various clinical barriers for in situ cancer vaccines. We also provide our perspective on this emerging field that lies at the interface of cancer vaccine biology and delivery technologies.
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Acknowledgements
M.J.M. acknowledges support from a US NIH Director’s New Innovator Award (no. DP2TR002776), a Burroughs Wellcome Fund Career Award at the Scientific Interface (CASI), the American Cancer Society (RSG-22-122-01-ET) and an NSF CAREER Award (no. CBET-2145491).
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N.G., M.-G.A., D.W. and M.J.M. developed the concept, researched data and wrote the article. R.E.-M. and L.X. contributed substantially to discussion of the content. R.E.-M. helped with language and figure modifications. All authors reviewed and edited the manuscript before submission.
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D.W. is named on patents that describe the use of nucleoside modified as a platform to deliver therapeutic proteins and vaccines. M.J.M, N.G., D.W. and M.-G.A. are named on patents describing the use of lipid nanoparticles and lipid compositions for nucleic acid delivery. The other authors declare no competing interests.
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Glossary
- Adjuvant
-
A substance that enhances the immune response to an antigen with which it is mixed.
- Antigen-presenting cells
-
(APCs). Immune cells that process antigens and display their peptide fragments on the cell surface together with molecules required for T cell activation. The main APCs for T cells are dendritic cells, macrophages and B cells.
- Cytokines
-
Secreted proteins that act on specific cytokine receptors to affect cellular behaviour. Cytokines made by lymphocytes are often called lymphokines or interleukins.
- Enhanced permeability and retention effect
-
(EPR effect). An effect defined by the heightened build-up of macromolecules, including liposomes, drugs and nanoparticles, in tumours compared with normal tissues. This phenomenon occurs because the blood vessels in tumour areas are permeable and the lymphatic system is impaired.
- Immune checkpoint
-
Inhibitory regulator of the immune system that is crucial to maintain self-tolerance, prevent autoimmunity and control the duration and extent of immune response to minimize collateral tissue damage. Immune checkpoint proteins are often overexpressed on tumour cells and compromise the antitumour immune response.
- Immune escape
-
The growth and metastasis of tumours by avoiding recognition and attack by the immune system through various mechanisms.
- Immune surveillance
-
The detection and elimination of tumours by lymphocytes specific for tumour antigens.
- Pattern recognition receptors
-
Proteins capable of recognizing molecules frequently found in pathogens (pathogen-associated molecular patterns; PAMPs) or molecules released by damaged cells (damage-associated molecular patterns; DAMPs).
- Stimuli-responsive materials
-
Materials that are capable of altering their chemical and/or physical properties upon exposure to external stimuli.
- T cell exhaustion
-
The gradual loss of T cell effector function and memory characteristics that occurs under continuous antigen exposure.
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Gong, N., Alameh, MG., El-Mayta, R. et al. Enhancing in situ cancer vaccines using delivery technologies. Nat Rev Drug Discov 23, 607–625 (2024). https://doi.org/10.1038/s41573-024-00974-9
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DOI: https://doi.org/10.1038/s41573-024-00974-9
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