# NIH grant: Design and development of a B7H3-targeting fluorescent probe for fluorescence-guided surgery of sarcoma (1R01CA317217-01) — retained record

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NIH grant 1R01CA317217-01: Design and development of a B7H3-targeting fluorescent probe for fluorescence-guided surgery of sarcoma
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: Aaron M. Mohs. Award: $577854.
Start: 2026-08-01T00:00:00.
PROJECT SUMMARY
Soft tissue sarcomas (STS) are mesenchymal cancers with >50 subtypes. Wide local excision (WLE)—removal
of the primary tumor with a layer of non-cancerous tissue surrounding it—is required for curative local control.
However, surgeons fail to achieve WLE in up to 34% of patients, with recurrence occurring in nearly half of these
patients and negative survival effects. Thus, intraoperative recognition of positive margins and immediate
removal of residual STS would significantly improve outcomes for patients with STS. Fluorescence-guided
surgery—paired with cancer-targeted optical probes—have enabled real-time intraoperative cancer
identification, tumor margin assessment, and removal of residual disease. FGS efficacy is optimized when
contrast agents have high tumor-to-background contrast. On-going clinical trials with existing agents targeting
the epidermal growth factor (EGFR) have demonstrated feasibility for FGS in STS, but results were
underwhelming due to inconsistent EGFR expression between patients and intratumoral EGFR heterogeneity.
More recent human data demonstrates high expression of the transmembrane protein B7-H3, an immune
checkpoint protein, in STS. Antibodies targeting B7-H3, such as enoblituzumab (MGA271), are being
investigated as therapeutics towards B7-H3-expressing solid tumors. In a collaborative effort, we conjugated
MGA271 to IRDye800 and deployed the resulting compound in our established rodent models of human STS
xenografts; contrast and tumor specificity results are promising. Our team has extensive experience in
developing targeted fluorescence imaging agents for FGS, including STSs. Herein, we will expand the
development of B7-H3-targeting antibody-fluorophore conjugates. We believe these conjugates will be strong
candidates for preclinical development due to consistent B7-H3 expression in STS and the availability of mAbs
targeting B7-H3 in clinical trials. We hypothesize that NIR fluorophore-antiB7-H3 mAb conjugates will bind to B7-
H3-overexpressing STSs and provide strong contrast enhancement to guide surgical resection. Therefore, the
goal of this proposal is to perform a thorough preclinical evaluation of NIR fluorescent conjugates of B7-
H3-targeting antibodies for FGS of STS. This goal will be addressed by three specific aims: (1) To develop
fluorescence-guided surgery probes that target B7-H3 using antibody-derived targeting ligands; (2) To establish
the safety and in vivo dynamics of fluorescently labelled B7-H3-targeting agents; and (3) To evaluate the
preclinical surgical efficacy of fluorescently-labelled B7-H3 targeting agents in orthotopic models of sarcoma.
Animal models are required due to the complexity of factors affecting tumor and tissue/organ accumulation of
contrast agents and to evaluate the complex factors of FGS for surgical oncology. Completion of this research
project will produce FGS contrast agents that detect and guide removal of STS and accomplish a pivotal step
towards future clinical development of a targeted probe for FGS of STS.
```



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