1 research outputs found
Imaging PD-L1 Expression with ImmunoPET
High sensitivity
imaging tools could provide a more holistic view
of target antigen expression to improve the identification of patients
who might benefit from cancer immunotherapy. We developed for immunoPET
a novel recombinant human IgG1 (termed C4) that potently binds an
extracellular epitope on human and mouse PD-L1 and radiolabeled the
antibody with zirconium-89. Small animal PET/CT studies showed that <sup>89</sup>Zr-C4 detected antigen levels on a patient derived xenograft
(PDX) established from a non-small-cell lung cancer (NSCLC) patient
before an 8-month response to anti-PD-1 and anti-CTLA4 therapy. Importantly,
the concentration of antigen is beneath the detection limit of previously
developed anti-PD-L1 radiotracers, including radiolabeled atezolizumab.
We also show that <sup>89</sup>Zr-C4 can specifically detect antigen
in human NSCLC and prostate cancer models endogenously expressing
a broad range of PD-L1. <sup>89</sup>Zr-C4 detects mouse PD-L1 expression
changes in immunocompetent mice, suggesting that endogenous PD-1/2
will not confound human imaging. Lastly, we found that <sup>89</sup>Zr-C4 could detect acute changes in tumor expression of PD-L1 due
to standard of care chemotherapies. In summary, we present evidence
that low levels of PD-L1 in clinically relevant cancer models can
be imaged with immunoPET using a novel recombinant human antibody