# NCI Early-stage Surgeon Scientist Program (ESSP)

> **NIH NIH P30** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2024 · $220,940

## Abstract

PROJECT ABSTRACT (Application submitted in response to NOSI NOT-CA-21-100)
 Colorectal cancer (CRC) with peritoneal metastases (PM) has evolved from a terminal
diagnosis to a condition treatable through cytoreductive surgery. Observed in up to 10-15% of
patients undergoing surgery for CRC and ultimately seen in up to 35% of patients with CRC,
cytoreductive surgery has revolutionized the treatment of patients with CRC-PM. A critical factor
predictive of oncologic outcomes after a cytoreductive surgery is the completeness of
cytoreduction; failure to do so is associated with earlier recurrence and poor survival. Current
methods of detection during surgery rely on visual and tactile inspection, posing challenges in
achieving complete cytoreduction. There is a critical need for improved methods of cancer
detection and treatment in the surgical setting.
 In response, new approaches such as in-vivo macroscopic immunohistochemical staining
using tumor-targeting fluorescent dyes for fluorescence image-guided surgery (FIGS) are in
development. FIGS helps identify tumor deposits, but its effectiveness is limited to surgically
removable lesions. Another approach, targeted photoimmunotherapy (PIT), combines a
phototoxic fluorophore with an anti-tumor targeting antibody to both identify and treat lesions. A
lead target for PIT is CEA, as it is specifically overexpressed in many gastrointestinal cancers,
especially CRC. An ideal candidate for this approach is carcinoembryonic antigen (CEA), a well-
studied tumor-marker overexpressed in many gastrointestinal cancers, particularly CRC. Its
specificity makes CEA an ideal target for our innovative approach, combining targeted
photoimmunotherapy (PIT) with fluorescence image-guided surgery (FIGS).
 Leveraging my expertise in fluorescence and surgery to develop theranostic approaches
along with a strong mentorship team, I propose to conduct a series of initial studies to determine
efficacy of PIT for FIGS and immune activation using CEA as the target. I hypothesize that a
humanized antibody targeting CEA (M5A) conjugated to the phototoxic fluorophore
(IRDye700DX) can effectively label CEA-expressing CRC for FIGS and upon NIR light activation,
induce phototoxic tumor-cell lysis, and elicit a cell-mediated immune response. This novel
approach aims to enhance surgical precision, offer local therapy in surgically challenging areas,
and potentially activate therapeutic immune responses. It could transform an immunosuppressive
microenvironment into an immune-activated one, significantly improving patient outcomes in
CRC-PM with minimal side effects and potential immune activation.

## Key facts

- **NIH application ID:** 10999222
- **Project number:** 3P30CA033572-41S1
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** JOHN D. CARPTEN
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $220,940
- **Award type:** 3
- **Project period:** 1997-08-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999222

## Citation

> US National Institutes of Health, RePORTER application 10999222, NCI Early-stage Surgeon Scientist Program (ESSP) (3P30CA033572-41S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10999222. Licensed CC0.

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