# Clinical Translation of a Novel Diagnostic Agent to Predict Immunotherapy Response in Solid Tumors

> **NIH NIH R44** · CYTOSITE BIOPHARMA, INC. · 2020 · $774,682

## Abstract

Over the past three years an entirely new cancer treatment paradigm has emerged following the FDA
approval of 6 different checkpoint inhibitors for a number of indications including; metastatic melanoma
and non-small cell lung cancer. These new agents work by effectively releasing the brakes on the
immune system that normally limit the body’s natural responses to tumor cells and have generated
long-term remission, and even some cures, However, the development, application and potential of
these new treatments is hindered by relatively low response rates and the long-times required to
ascertain objective responses. Immunotherapy is expensive and comes with serious potential side
effects, so early selection of the most effective therapy for each patient is critical. Currently, there is no
effective way to measure response, as traditional methods such as biopsy and anatomic imaging have
not been predictive. To overcome these limitations, we have developed a molecular imaging agent for
Positron Emission Tomography (PET) that is targeted to granzyme B, the enzyme released by activated
immune cells to kill target tumor cells. By non-invasively measuring the tumor concentration of
granzyme B, we have shown the specificity and potential of our PET imaging agent to predict early
response to checkpoint inhibitors with in vivo non-clinical cancer models. We have extended our work
ex vivo specificity analysis in human cancer tissue to demonstrate our target shows granzyme B levels
are predictive of response in melanoma patient samples. Given the preliminary success of our agent to
determine immunotherapy response and the lack of effective alternatives, we believe an accelerated
translation to human testing is warranted. This SBIR proposal includes the preparation and completion
of an exploratory-IND study to demonstrate safety in a small group of Melanoma patients and to
determine safety, distribution and imaging potential in humans undergoing checkpoint inhibitor
therapy. Although, this study cannot be empowered to determine efficacy, PET imaging data will be
correlated with clinical follow up and melanoma biopsy data as a gold-standard for Immuno-Oncology
responders vs non-responders.

## Key facts

- **NIH application ID:** 10017924
- **Project number:** 5R44CA228855-03
- **Recipient organization:** CYTOSITE BIOPHARMA, INC.
- **Principal Investigator:** JAMES F KRONAUGE
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $774,682
- **Award type:** 5
- **Project period:** 2018-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017924

## Citation

> US National Institutes of Health, RePORTER application 10017924, Clinical Translation of a Novel Diagnostic Agent to Predict Immunotherapy Response in Solid Tumors (5R44CA228855-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10017924. Licensed CC0.

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