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Artificial Antigen Presenting Cell aAPC Mediated Activation and Expansion of Natural Killer T Cells
Published on: December 29, 2012
Augmenting Granzyme B-Expressing NK Cells by Invariant NKT Ligand-Loaded APCs in Patients with Postoperative Early
Tomonori Iyoda1, Kanako Shimizu1,2, Masami Kawamura1
1Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Abstract:
NK cells are major effector cells involved in the elimination of early tumors and prevent metastasis. They often have an impaired function in patients with cancer. Preclinical studies have demonstrated NK cell activation as the adjunctive effect of invariant NKT (iNKT) cells. Activation of iNKT cells after administration of the glycolipid ligand α-galactosylceramide, loaded with CD1d-expressing human PBMC-derived APCs (APC/Gal), is an attractive cancer therapy to optimize the use of NK cells. However, the subsets of NK cells that are activated following iNKT cell activation as well as the period of NK cell activation remain unclear. In this study, we report that the granzyme B-expressing NK cell response in postoperative lung cancer patients was enhanced 49 d after administration of APC/Gal in a phase II study. We found maximum IFN-γ production on day 49 in 13 out of 27 APC/Gal-treated patients. On day 49, 14 out of 27 patients (51.9%) had higher IFN-γ production by iNKT cells (>6-fold higher than the baseline level). This increment significantly correlated with granzyme B-expressing NK cells. Although IFN-γ production was lower in patients in the nontreated group, we detected maximum IFN-γ production 12 mo after the resection of lung cancer (9 out of 29 patients [31%]). These findings suggest that elimination of cancer cells leads to increased NK cell function, which can be further enhanced by APC/Gal therapy.
Insights
Invariant natural killer T (iNKT) cell therapy using APC/Gal enhanced natural killer (NK) cell function in lung cancer patients. This immunotherapy boosted granzyme B and IFN-γ production, suggesting improved cancer elimination.
Area of Science:
- Immunology
- Oncology
- Cancer Therapy
Background:
- Natural killer (NK) cells are crucial for early tumor elimination and metastasis prevention, but their function is often impaired in cancer patients.
- Preclinical studies suggest that invariant NKT (iNKT) cells can activate NK cells, offering a potential therapeutic strategy.
- The specific NK cell subsets activated by iNKT cells and the duration of this activation remain largely unknown.
Purpose of the Study:
- To investigate the impact of invariant NKT (iNKT) cell activation on NK cell function in postoperative lung cancer patients.
- To determine the specific NK cell responses and the timing of activation following APC/Gal therapy.
Main Methods:
- A phase II clinical study involving postoperative lung cancer patients treated with APC/Gal (α-galactosylceramide loaded with CD1d-expressing human PBMC-derived APCs).
- Monitoring of granzyme B expression and interferon-gamma (IFN-γ) production in NK and iNKT cells at various time points post-treatment.
- Comparison of immune responses between APC/Gal-treated patients and a non-treated control group.
Main Results:
- APC/Gal therapy significantly enhanced granzyme B-expressing NK cell response by day 49 in lung cancer patients.
- Maximum IFN-γ production by iNKT cells was observed on day 49 in a majority of treated patients (51.9%), correlating with increased NK cell activity.
- While IFN-γ production increased naturally over time in non-treated patients, APC/Gal therapy demonstrated a more pronounced and timely enhancement of immune cell function.
Conclusions:
- APC/Gal therapy effectively enhances NK cell function, specifically granzyme B and IFN-γ production, in postoperative lung cancer patients.
- The study identifies day 49 as a key time point for observing maximal immune enhancement after APC/Gal administration.
- These findings support APC/Gal therapy as a promising approach to optimize NK cell-mediated cancer immunotherapy.
