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Recruiting Natural Killer T Cells to Improve Vaccination: Lessons from Preclinical and Clinical Studies
Olivia K Burn1, Nathaniel Dasyam1, Ian F Hermans1
1Malaghan Institute of Medical Research, Wellington, New Zealand.
Abstract:
The capacity of type I natural killer T (NKT) cells to provide stimulatory signals to antigen-presenting cells has prompted preclinical research into the use of agonists as immune adjuvants, with much of this work focussed on stimulating T cell responses to cancer. In attempting to evaluate this approach in the clinic, our recent dendritic-cell based study failed to show an advantage to adding an agonist to the vaccine. Here we present potential limitations of the study, and suggest why other simpler strategies may be more effective. These include strategies to target antigen-presenting cells in the host, either through promoting efficient transfer from injected cell lines, facilitating uptake of antigen and agonist as injected conjugates, or encapsulating the components into injected nanovectors. While the vaccine landscape has changed with the rapid uptake of mRNA vaccines, we suggest that there is still a role for recruiting NKT cells in altering T cell differentiation programmes, notably the induction of resident memory T cells.
Insights
Adding agonists to dendritic cell vaccines did not improve cancer immunity in a clinical trial. Simpler strategies targeting antigen-presenting cells may be more effective for immune stimulation.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Type I natural killer T (NKT) cells stimulate antigen-presenting cells, leading to preclinical research on agonists as immune adjuvants for cancer vaccines.
- NKT cell agonists have been explored to enhance T cell responses against cancer.
Purpose of the Study:
- To evaluate the clinical efficacy of adding an NKT cell agonist to a dendritic cell-based vaccine.
- To identify limitations of previous studies and propose alternative strategies for immune stimulation.
Main Methods:
- A clinical trial involving a dendritic cell-based vaccine with and without an NKT cell agonist.
- Analysis of potential limitations and alternative strategies for targeting antigen-presenting cells.
Main Results:
- The addition of an NKT cell agonist to the dendritic cell vaccine did not demonstrate a significant advantage in stimulating T cell responses.
- The study identified potential limitations in the clinical application of NKT cell agonists.
Conclusions:
- Simpler strategies, such as targeting antigen-presenting cells directly or using nanovectors, may be more effective than current agonist-based approaches.
- Despite advancements in mRNA vaccines, NKT cells may still play a role in modulating T cell differentiation and inducing resident memory T cells.
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