# A micro-dissection platform for generating uniform-sized patient-derived tumor organoids (PDOs) for personalized cancer therapy

> **NIH NIH R21** · STANFORD UNIVERSITY · 2023 · $179,337

## Abstract

Project Summary
Patient-derived tumor organoids (PDO), involving the ex vivo culture of fresh tumor fragments,
have emerged as promising models for predicting patient drug response for personalized cancer
therapy. PDOs recapitulate the tumor micro-environment (TME), resemble the source tumor
phenotypically and genomically, and are compatible with high-throughput drug screening.
However, the lack of preservation of immune cells in PDOs has been a major roadblock to
modeling immunotherapy. Our team recently demonstrated a new type of PDO that cultures tumor
fragments as a cohesive unit, allowing the in situ preservation of diverse immune cell types
alongside tumor cells without artificial reconstitution. This approach has enabled the modeling of
patient-specific responses to immune checkpoint inhibitors.
 One of the first steps in the generation of PDOs is the dissection of patient tumor specimen
into small fragments. Mechanical dissection, instead of enzymatic digestion, is critical in
preserving the in vivo association between tumor cells and endogenous immune and non-immune
elements. The ability to preserve endogenous immune cells, including tumor-infiltrating
lymphocytes (TIL), is particularly important for personalized immunotherapy testing.
 However, current mechanical dissection relies primarily on manual mincing of tumor specimen
into small fragments. It results in fragments with a broad size range, and is imprecise and
irreproducible. Fragments that are too large suffer from inadequate nutrient supply, suboptimal
oxygenation and viability, and poor drug penetration. Fragments that are too small are unlikely to
preserve sufficient stromal cells to support PDO growth, and/or endogenous immune cells which
may be present at low concentrations.
 As such, there is an unmet need for a better way to generate tumor fragments of controllable
and uniform size, and identify optimal size(s) to increase the reproducibility and yield of viable
PDOs that can preserve the cellular contexture and tumor architecture. This project aims to
address this need by developing a new method to mechanically dissect tumor specimen into
uniform fragments. Performance measures include fragment size uniformity, PDO viability,
preservation of immune cells, and tumor cytotoxicity in response to immunotherapy. Other cutting
methods including manual mincing will be used as benchmarks.

## Key facts

- **NIH application ID:** 10697348
- **Project number:** 5R21CA261643-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sindy Kam-Yan Tang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $179,337
- **Award type:** 5
- **Project period:** 2022-09-05 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10697348

## Citation

> US National Institutes of Health, RePORTER application 10697348, A micro-dissection platform for generating uniform-sized patient-derived tumor organoids (PDOs) for personalized cancer therapy (5R21CA261643-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10697348. Licensed CC0.

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