# Targeted radiation and immunocytokine therapy for CEA positive malignancies

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2023 · $676,263

## Abstract

SUMMARY/ABSTRACT
Image guided radiotherapy (IGRT) or systemically administered radionuclide therapy are attractive approaches
that can perturb the tumor microenvironment (TME) so that targeted immunotherapy can convert a largely
immunoresistant into an immunosusceptible tumor. Although this approach has been clinically explored using
high or low or high plus low dose IGRT plus untargeted checkpoint immunotherapy, further improvements are
warranted and require testing in appropriate clinical studies and preclinical models. In this application we
propose three aims to test our hypothesis that IGRT and or targeted alpha therapy (TAT) followed immediately
by immunocytokine (ICK), a form of targeted immunotherapy, will lead to increased tumor infiltration of IFN+
CD8s (Teff) and decreased Foxp3+ CD4s (Treg). This hypothesis is supported by two studies targeting CEA,
a major marker of solid tumor malignancies (eg. colon and breast), in CEA transgenic mice that are
immunocompetent, express CEA in normal tissues, and are tolerant to CEA. We now propose to test this
hypothesis in two clinical trials, aims 1 (IGRT + ICK) and 2 (TAT), and perform immunocorrelate studies for
Teff and Treg cells, among others, on pre- and post-therapy biopsies. Aim 2 is a TAT only study as a prelude
to a third clinical trial combining TAT plus ICK, that will be initiated at the end of the project period. In aim 3, we
will refine our animal studies to determine TME changes immediately after sequential therapy for both IGRT
plus ICK or TAT plus ICK, by a combination of PET imaging for CEA, CD8s and stromal cells by fibroblast
activated protein (FAPI), along with flow and IHC analysis of tumors, LNs and spleen. We expect the results of
aims 1 and 2 to further guide aim 3, and the results of aim 3 to guide future trials that incorporate IGRT and/or
TAT plus ICK in CEA positive malignancies.

## Key facts

- **NIH application ID:** 10720201
- **Project number:** 1R01CA283603-01
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** John Ernest Shively
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $676,263
- **Award type:** 1
- **Project period:** 2023-09-21 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10720201

## Citation

> US National Institutes of Health, RePORTER application 10720201, Targeted radiation and immunocytokine therapy for CEA positive malignancies (1R01CA283603-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10720201. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*