期刊
JOURNAL OF NUCLEAR MEDICINE
卷 62, 期 11, 页码 1638-1644出版社
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.120.258871
关键词
cancer; nuclear imaging; single domain antibody; Nano-body; immune checkpoint; LAG-3
资金
- Belgian Foundation against Cancer, Kom op tegen Kanker (Stand Up to Cancer)
- Flemish Cancer Society
- Research Foundation Flanders (FWO-V) [1501019N, I001618N]
- Emmanuel Vanderschueren award
- FWO-SB fellow [1S24218N]
- Precirix
Recent advances in immune-oncology have led to the discovery of next-generation immune checkpoints, with LAG-3 being a prime target for cancer treatment. Utilizing single-domain antibodies for molecular imaging allows for noninvasive monitoring of LAG-3 expression on tumor-infiltrating lymphocytes, which could be crucial for predicting therapy outcomes.
Recent advances in the field of immune-oncology led to the discovery of next-generation immune checkpoints (ICPs). Lymphocyte activation gene-3 (LAG-3), being the most widely studied among them, is being explored as a target for the treatment of cancer patients. Several antagonistic anti-LAG-3antibodies are being developed and are prime candidates for clinical application. Furthermore, validated therapies targeting cytotoxic T-lymphocyte-associated protein-4, programmed cell-death protein-1, or programmed cell-death ligand-1 showed that only subsets of patients respond. This finding highlights the need for better tools for patient selection and monitoring. The potential of molecular imaging to detect ICPs noninvasively in cancer is supported by several preclinical and clinical studies. Here, we report on a single-domain antibody to evaluate whole-body LAG-3 expression in various syngeneic mouse cancer models using nuclear imaging. Methods: SPECT/CT scans of tumor-bearing mice were performed 1 h after injection with radiolabeled single-domain antibody. Organs and tumors of mice were isolated and evaluated for the presence of the radiolabeled tracer and LAG-3-expressing immune cells using a gamma-counter and flow cytometry respectively. PD-1/LAG-3-blocking antibodies were injected in MC38-bearing mice. Results: The radiolabeled single-domain antibody detected LAG-3 expression on tumor-infiltrating lymphocytes (TILs) as soon as 1 h after injection in MC38, MO4, and TC-1 cancer models. The single-domain antibody tracer visualized a compensatory upregulation of LAG-3 on TILs in MC38 tumors of mice treated with PD-1-blocking antibodies. When PD-1 blockade was combined with LAG-3 blockade, a synergistic effect on tumor growth delay was observed. Conclusion: These findings consolidate LAG-3 as a next-generation ICP and support the use of single-domain antibodies as tools to noninvasively monitor the dynamic evolution of LAG-3 expression by TILs, which could be exploited to predict therapy outcome.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据