Granzyme B PET Imaging in Response to In Situ Vaccine Therapy Combined with αPD1 in a Murine Colon Cancer Model
Siddesh V. Hartimath,
Boominathan Ramasamy,
Tan Yun Xuan,
Tang Jun Rong,
Shivashankar Khanapur,
Peter Cheng,
You Yi Hwang,
Edward G. Robins,
Julian L. Goggi
Affiliations
Siddesh V. Hartimath
Laboratory of Radiochemistry & Molecular Imaging (LRMI), Institute of Bioengineering and Bioimaging (IBB), A*STAR Research Entities, Helios, Singapore 138667, Singapore
Boominathan Ramasamy
Laboratory of Radiochemistry & Molecular Imaging (LRMI), Institute of Bioengineering and Bioimaging (IBB), A*STAR Research Entities, Helios, Singapore 138667, Singapore
Tan Yun Xuan
Laboratory of Radiochemistry & Molecular Imaging (LRMI), Institute of Bioengineering and Bioimaging (IBB), A*STAR Research Entities, Helios, Singapore 138667, Singapore
Tang Jun Rong
Laboratory of Radiochemistry & Molecular Imaging (LRMI), Institute of Bioengineering and Bioimaging (IBB), A*STAR Research Entities, Helios, Singapore 138667, Singapore
Shivashankar Khanapur
Laboratory of Radiochemistry & Molecular Imaging (LRMI), Institute of Bioengineering and Bioimaging (IBB), A*STAR Research Entities, Helios, Singapore 138667, Singapore
Peter Cheng
Laboratory of Radiochemistry & Molecular Imaging (LRMI), Institute of Bioengineering and Bioimaging (IBB), A*STAR Research Entities, Helios, Singapore 138667, Singapore
Laboratory of Radiochemistry & Molecular Imaging (LRMI), Institute of Bioengineering and Bioimaging (IBB), A*STAR Research Entities, Helios, Singapore 138667, Singapore
Julian L. Goggi
Laboratory of Radiochemistry & Molecular Imaging (LRMI), Institute of Bioengineering and Bioimaging (IBB), A*STAR Research Entities, Helios, Singapore 138667, Singapore
Immune checkpoint inhibitors (ICIs) block checkpoint receptors that tumours use for immune evasion, allowing immune cells to target and destroy cancer cells. Despite rapid advancements in immunotherapy, durable response rates to ICIs remains low. To address this, combination clinical trials are underway assessing whether adjuvants can enhance responsiveness by increasing tumour immunogenicity. CpG-oligodeoxynucleotides (CpG-ODN) are synthetic DNA fragments containing an unmethylated cysteine-guanosine motif that stimulate the innate and adaptive immune systems by engaging Toll-like receptor 9 (TLR9) present on the plasmacytoid dendritic cells (pDCs) and B cells. Here, we have assessed the ability of AlF-mNOTA-GZP, a peptide tracer targeting granzyme B, to serve as a PET imaging biomarker in response to CpG-ODN 1585 in situ vaccine therapy delivered intratumourally (IT) or intraperitoneally (IP) either as monotherapy or in combination with αPD1. [18F]AlF-mNOTA-GZP was able to differentiate treatment responders from non-responders based on tumour uptake. Furthermore, [18F]AlF-mNOTA-GZP showed positive associations with changes in tumour-associated lymphocytes expressing GZB, namely GZB+ CD8+ T cells, and decreases in suppressive F4/80+ cells. [18F]AlF-mNOTA-GZP tumour uptake was mediated by GZB expressing CD8+ cells and successfully stratifies therapy responders from non-responders, potentially acting as a non-invasive biomarker for ICIs and combination therapy evaluation in a clinical setting.
