Engineered antibody fragments for immuno-PET imaging of endogenous CD8 ⁺ T cells in vivo

Abstract

Significance Anti-CD8 immuno-PET imaging agents provide the potential to monitor the localization, migration, and expansion of CD8-expressing cells noninvasively in vivo. Shown here is the successful generation of functional anti-CD8 imaging agents based on engineered antibodies for use in a variety of preclinical disease and immunotherapeutic models.

64 Cu antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET

“…However, the transferred cells could be only detected at the injection site and not systemically. An optimization of our cell-labeling approach might involve mAb fragments (26,27), which carry fewer radionuclides, and thus induce less damage to their target cells. Furthermore, the missing Fc-part of the mAbs would likely prevent the Fcreceptor-mediated cellular cytotoxicity in vivo, thereby increasing the safety of a possible clinical translation.…”

“…Furthermore, the missing Fc-part of the mAbs would likely prevent the Fcreceptor-mediated cellular cytotoxicity in vivo, thereby increasing the safety of a possible clinical translation. The successful use of mAb fragments to detect immune cells in vivo was shown in the study by Tavaré et al (27). The authors generated 64 Cu-labeled anti-CD8 antibody fragments to detect CD8 + T cells in lymphatic structures in immune competent mice.…”

Enzyme‐Mediated Modification of Single‐Domain Antibodies for Imaging Modalities with Different Characteristics

“…There are now tools to track immune cells, by the use of isotopically labeled anti-CD11b, anti-Class-II-MHC, and anti-CD8 antibody fragments. [5][6][7] The comparatively large size of intact full-sized antibodies results in a long circulatory halflife, and may also hinder efficient tissue penetration. [8] These considerations have driven the search for smaller antibody-derived formats as alternative imaging tools.…”

“…[8] These considerations have driven the search for smaller antibody-derived formats as alternative imaging tools. [1,6] We generated camelid single-domain antibody fragments (VHHs) as the smallest antigen-binding derivatives obtainable from naturally occurring antibodies. [9] VHHs lend themselves to enzymatic modification and have been used in a variety of applications, including imaging.…”

Imaging the multiple facets of immuno-oncology

“…Antibodies as well as small molecules that target PD-L1 have been developed and are being studied in animal models as well as in the clinic [10,11]. Clinical trials are also currently on-going with a radiolabeled minibody that targets CD8-positive cells [12], whose recruitment to the tumor is believed critical to successful therapy. Other putative cytokines expressed by leukocyte cell populations that are recruited to the tumor site (upon successful blockade of the checkpoint), including particularly granzyme B [13], expressed by activated macrophages, are also being evaluated in preparation for clinical study.…”