Imaging Checkpoint Molecules with sdAbs

Single domain antibodies (sdAbs) have proved to be excellent candidates for imaging of checkpoint molecules within the tumor microenvironment. The pharmacokinetic properties of sdAb-based imaging agents, as well as the nature of the epitopes they recognize, may be useful attributes to capture the dynamics of the checkpoint molecules and the anti-tumor response under immunotherapy. Armed with rich experience in sdAb development and immune checkpoints research, Creative Biolabs provides customized services or products concerning noninvasive imaging of the immune checkpoint using sdAbs, from development to pre-clinical use.

Why Targeting Checkpoint Molecules with sdAbs?

Immune checkpoint inhibition is a promising cancer therapy, which has progressed rapidly from a preclinical concept to clinical implementation. Commonly considered checkpoint molecules are CTLA-4, PD-1/PD-L1, and LAG-3, and the list grows. Immune checkpoint blockade revolutionized anti-cancer therapy but unfortunately, only a subset of patients can benefit from it. The development of innovative and efficacious diagnostic methods is warranted. Thus, there is growing interest to do this noninvasively, by molecular imaging with target-specific tracers. SdAbs are small antigen-binding moieties that efficiently penetrate cell-cell interfaces in tumors and generate high contrast in noninvasive imaging, making them prime candidates for the development of novel imaging tracers.

Fig.1 Illustration of the immune checkpoint molecules and their inhibitors. (Rossi, 2019)

Popular Targets

PD-L1

Whole-body non-invasive imaging of PD-L1, which can provide visualization, localization and quantification of its expression throughout the body, is likely to be more informative and holds better prognostic value compared with immunohistochemistry (IHC). An anti-mouse PD-L1 sdAb (B3) was developed and labeled site-specifically with ¹⁸F. PET using the ¹⁸F-labeled anti-PD-L1 sdAb readily detected the B16 melanoma. An anti-human PD-L1 sdAb (sdAb K2) was also developed and used to non-invasively image mice bearing a tumor xenograft. The images showed high signal-to-noise ratios in tumors and detected PD-L1 in melanoma and breast tumors.

CTLA-4

In a previous study, a radiolabeled anti-CTLA-4 sdAb (H11) was used to non-invasively image CTLA-4 expression in a B16 melanoma model treated with anti-CTLA-4 antibody by PET. Scientists finally found that accessible CTLA-4 is largely confined to the tumor.

LAG3

LAG-3 is an inhibitory checkpoint molecule on T cells. Given the importance of LAG-3, anti-LAG-3 sdAbs have been developed and used for non-invasive imaging. The ^99mTc-labeled sdAbs showed specific uptake in secondary lymphoid organs, and no signal was detected in LAG-3 knockout mice. LAG-3 expression was confirmed by flow cytometry and immunohistochemistry analyses and correlated well with the SPECT images.

Customized Services

• Generation and in vitro characterization of sdAb
• Nanotracers construction services
• In vitro assessment services
• In vivo imaging services
• Statistical analysis

As shown by the multitude of different sdAb-based imaging tools with promising pre-clinical effects reported in the last years, sdAb rises as very potent imaging agents. If you are interested in customized imaging services or products development, please feel free to contact us for more information.

Reference

1. Rossi, J. F.; et al. Immune precision medicine for cancer: a novel insight based on the efficiency of immune effector cells. Cancer Communications. 2019, 39(1): 34.

For Research Use Only.