# Bioreactor for Manufacturing Chemotactically Competent Immune Cell Therapies

> **NIH NIH R61** · SRI INTERNATIONAL · 2024 · $375,016

## Abstract

PROJECT SUMMARY
Current cell expansion procedures for antigen-specific CAR T cells and CAR NK cells result in cells with
a broad repertoire of chemokine receptors. Upon infusion, they migrate to off-tumor healthy tissues and
exert toxicities by targeting antigens expressed at basal levels. The ability to produce therapeutic cells
with affinity to migrate into the tumor microenvironment (TME) is a critical unmet need. The investigating
team’s mission is to harness the immune system to treat solid tumors. In line with this mission, the
objectives of this R61 are to 1) develop a prototype of the bioreactor to selectively culture chemotactically
competent cell-based therapies (CAR T, CAR NK-92), and 2) demonstrate use of this subset for
migrating through a tissue-mimicking barrier and kill epithelial ovarian cancer cells in an antigen-specific
manner. The rationale for this effort is that it will disrupt the status quo of current cell manufacturing
technology, which generates therapeutic cells that traffic not only to tumors but also to healthy tissue.
The team will conduct the R61 project under two milestone-driven aims: 1) Develop bioreactor for
generating chemotactically competent CAR NK-92 cells; 2) Demonstrate utility of the bioreactor for
generating chemotactically competent CAR T cells. In a follow-on R33, the team will use the bioreactor to
scale up the production of these chemotactically competent cell therapies for preclinical mouse studies.
The impact of bioreactor will be in making treatments safer (by mitigating off-tumor migration of
therapeutic cells) and affordable (by reducing manual intervention in the closed-system bioreactor).
Mitigating off-tumor migration will reduce the burden of manufacturing because most of the therapeutic
cells will reach the target TME site. The significance of this project is also supported by its applicability to
other immune cells (CAR NK cells, CAR macrophages) that are currently in development for targeting
solid tumors.

## Key facts

- **NIH application ID:** 10818058
- **Project number:** 1R61CA281785-01A1
- **Recipient organization:** SRI INTERNATIONAL
- **Principal Investigator:** Xiaohe Liu
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,016
- **Award type:** 1
- **Project period:** 2024-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818058

## Citation

> US National Institutes of Health, RePORTER application 10818058, Bioreactor for Manufacturing Chemotactically Competent Immune Cell Therapies (1R61CA281785-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10818058. Licensed CC0.

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