# Autoantibody-based early detection of small-cell lung cancer by immunoimaging

> **NIH NIH F32** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $62,084

## Abstract

Project Summary/Abstract
Small-cell lung cancer (SCLC) is an aggressive and deadly cancer. Over 2/3 of SCLC are diagnosed at later
stages, where patients are expected to survive for only 8-12 months with 5-year survival rates less than 7%.
Smoking increases the risk of developing SCLC by up to 100-fold. While annual lung cancer screening using
low-dose computed tomography (LDCT) can screen for other lung cancers, this modality is ineffective for
detecting SCLC at earlier stages, where interventions can increase 5-year survival rates to >54%. SCLC can
induce an autoimmune response, and our labs have shown a combined panel of 4 autoantibodies (AutoAb)
can successfully identify SCLC tumors up to a year prior to diagnosis, proving the utility of these markers to
identify and validate early SCLC in multiple sample sets. This fellowship proposal aims to develop antibody-
based positron emission tomography (immunoPET) probes against these markers as a secondary screening
method, allowing for earlier detection than is capable with current LDCT. Aim 1 explores the contribution of
post-translational modifications (e.g., glycosylation, isoaspartylation, and citrullination) that are upregulated in
cancer, including SCLC, to neopitopes recognized by these AutoAb, which may allow for more targeted
theranostics. Aim 2 will develop additional monoclonal antibodies (mAb) against candidate SCLC AutoAb
biomarkers to allow for a broad targeting of AutoAb differentially expressed in patient plasma. In Aim 3, these
mAb will be conjugated to an infrared fluorophore, that will be used as a proof of concept for immuno-imaging
of tumors in a murine model of SCLC using in vivo fluorescence and ex vivo immuno-fluorescence. The most
promising 1-2 markers/mAb will then be developed into zirconium-89 conjugated immunoPET probes. Thus, it
is envisioned that SCLC patients will be identified with an AutoAb blood test with tumor
confirmation/localization with immunoPET tracers against SCLC AutoAb markers. This ultimately combines the
sub-picomolar sensitivity of PET and sub-millimeter spatial resolution of CT with the high affinity and specificity
of antibodies, allowing for detection of smaller, and thus less advanced, tumors that allow for earlier and more
effective therapeutic interventions. Given the recalcitrant nature of SCLC and the difficulty of its identification
via conventional CT, this proposed research aligns well the NCI’s scientific priority to detect and diagnose
cancer when treatment is most effective. This fellowship training will allow the applicant to build upon existing
cancer research skills, gaining complementary experience in 1) identifying post-translational modifications and
the roles these play in neoantigen formation, 2) generating plasmids/recombinant proteins and development of
mAbs, 3) mouse models of SCLC, 4) antibody-based PET tracers, 5) in vivo small animal translational imaging
(luciferase, fluorescence, and PET), and 6) other professional devel...

## Key facts

- **NIH application ID:** 10233242
- **Project number:** 1F32CA261055-01
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Andrew George Kenro Kunihiro
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $62,084
- **Award type:** 1
- **Project period:** 2021-04-01 → 2022-03-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233242

## Citation

> US National Institutes of Health, RePORTER application 10233242, Autoantibody-based early detection of small-cell lung cancer by immunoimaging (1F32CA261055-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10233242. Licensed CC0.

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