# Engineered Antibodies as PET Probes for Monitoring Immunotherapy Responses

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $234,750

## Abstract

ABSTRACT: Malignant gliomas are deadly tumors in adults and children. Despite tumor resection and radiation
therapy (with or without chemotherapy), the prognosis is dismal. Immunotherapy may represent a promising
therapeutic strategy for gliomas; however, response rates to immunotherapies have been highly variable. Similar
to many other cancers, glioma immunotherapy trials typically continue until disease progression is apparent due
to a lack of informative biomarkers. Early monitoring of biologic responses can shorten the duration of ineffective
treatments and allow increased opportunities to attempt other therapies but will require accurate assessment of
effective biologic responses within the tumor. Novel approaches using immunoPET imaging of lymphocytes to
guide immunotherapy include quantification of total lymphocyte populations and lymphocyte activation, although
these do not inform on the actual killing of tumor cells. For example, lymphocyte accumulation or activation may
not lead to tumor killing when tumors become “invisible” to T-cells, are adoptively transferred, or in highly
immunosuppressed tumors. Therefore, development of novel tracers to quantify lymphocyte-mediated tumor
cytotoxicity as an early indicator or therapeutic response remains an unmet need. Therefore, we propose to
develop immunoPET probes that will unequivocally quantify the extent of cytotoxicity of the T-cells by targeting
a cell surface marker CD107a. Our long-term goal is to translation an anti-LGAM engineered antibody for
monitoring immunotherapy. The overall objective of this application is to develop novel CD107a-targeted
antibody fragments, Mb or Db, for comparison to a mouse Fc-modified anti-CD107a Mab, which can quantify
lytic degranulation. Therefore, our central hypothesis is that engineered antibodies will enable quantification of
an LGAM and monitoring of immunotherapeutic efficacy. The first aim is to bioengineer a Zr-89-anti-CD107a
Mab with species-specific Fc regions for the detection of lytic degranulation of lymphocytes in immunotherapy-
treated murine gliomas. The working hypothesis is that reducing serum clearance by increasing antibody affinity
for the neonatal Fc receptor will enhance tumor residence time, specific CD107a-mediated uptake, and
prediction of immunotherapy responses in gliomas. The second aim is to compare bioengineered Cu-64-labelled
minibody and diabody for monitoring lytic degranulation in murine gliomas following immunotherapy. The working
hypothesis is that despite faster clearance relative to IgG, the Mbs and Dbs will retain high CD107a-mediated
uptake, allow more frequent time points for longitudinal imaging, and enhanced prediction of immunotherapy
response in murine gliomas. Upon completion of the research proposed in this application, we expect to have
demonstrated that CD107a, a direct biomarker for the cytotoxic action of T-cells, is a viable target for immunoPET
for predicting therapeutic response in preclinical murin...

## Key facts

- **NIH application ID:** 10197929
- **Project number:** 5R21EB029650-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Wilson Barry Edwards
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $234,750
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197929

## Citation

> US National Institutes of Health, RePORTER application 10197929, Engineered Antibodies as PET Probes for Monitoring Immunotherapy Responses (5R21EB029650-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10197929. Licensed CC0.

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