Development and evaluation of the first-in-class nanobody based PET tracer targeting human inducible T-cell co-stimulator receptor

BACKGROUND: Inducible T-cell co-stimulator receptor (ICOS) is a conserved biomarker mainly expressed on activated T cells. It had been proved that PET imaging targeting ICOS was a promising strategy for assessment of immune responses in cancer immunotherapy. For further translating this strategy into clinic, in the present study, we had developed the first-in-class ICOS targeting nanobody ICOS-53 via alpaca immunization and yeast display screening. RESULTS: The binding affinity of ICOS-53 to recombinant ICOS protein was validated by surface plasmon resonance, and the KD value was 85.3 pM. ICOS-53 was then conjugated to NOTA and radiolabeled with [68Ga]GaCl3. In PET imaging study, higher accumulation of [68Ga]Ga-NOTA-ICOS-53 could be observed in CHO-ICOS (CHO transfected by human ICOS) tumors, compared to CHO (Chinese Hamster Ovary cells) cohort from all-time points examined. Statistically significant correlation between PET imaging quantitative results and biodistribution could be observed (R = 0.548, P = 0.00117). Immunofluorescence staining also confirmed the high ICOS expression in CHO-ICOS tumors. CONCLUSION: Our data demonstrated that we had developed a novel nanobody based PET tracer targeting human ICOS, [68Ga]Ga-NOTA-ICOS-53 PET imaging was a promising strategy for tracking ICOS+ cells both in vitro and in vivo.