# Time to ATTAC: Adoptive Transfer of T cells Against gp100+ Cells to treat LAM

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $605,116

## Abstract

SUMMARY
Lymphangioleiomyomatosis (LAM) is a rare disorder with devastating consequences for the young women
diagnosed with this disease. We observed occult expression of the glycoprotein gp100 and other melanoma
associated antigens in nodular, pulmonary tumor lesions. LAM cells carry a dysfunctional TSC complex and
exhibit constitutive mTOR activation. Though rapamycin can provide relief, there is a great need to develop a
true cure for women with LAM. We evaluated the expression of suitable antigens and the associated infiltration
by immune cells. Here we propose to capitalize on the occult expression of melanoma associated antigens to
develop safe and effective, T cell-based immunotherapy for LAM. First, we will generate constructs targeting
LAM antigens to transduce T cells and prepare the cells for adoptive transfer. These constructs are equipped or
not with a homing receptor to drive the adoptively transferred T cells to LAM lung, exploiting the consistent
overexpression of the chemokine ligand CCL2 within affected tissues., in order to minimize off tumor effects.
Transgenic T cells are generated with stem cell-like attributes to promote longevity and continued functionality.
Efficacy and safety comparisons are made between TCR transgenic and HLA-independent CAR T cells targeting
a LAM surface antigen. Based on expression of a natural receptor epitope encoded by the construct, resulting T
cells are readily sorted and traced, and will be put to the test in mouse models of the disease. We will engage
an immunocompetent disease model, as well as PDX implanted mice to explore the treatment potential of
adoptively transferred, LAM reactive T cells. Within PDX mice, the LAM microenvironment is well conserved.
Expression of LAM tumor antigens can be maintained over time, while therapeutics can be tested in a statistically
and biologically meaningful way. Finally, we will explore the immune microenvironment in LAM and in PDX
tissues exposed to adoptive transfer or not, to learn whether T cells harbored by LAM lung or supplied by
adoptive transfer can be taught to clear existing lesions. Next, our collaborative group aims to develop a winning
immunotherapeutic approach to treat the devastating disease. The project will thus cover (1) generating and in
vitro testing of transgenic mouse and human T cells; and (2) measuring the anti-tumor efficacy of adoptively
transferred T cells in immune competent as well as PDX models of LAM as well as (1) in-depth analysis of the
immune environment encountered in LAM lesions before and after adoptive transfer. Resulting preclinical data
can then serve to design a clinical trial in follow-up studies and test the hypothesis, that benign tumors in LAM
are amenable to treatment by adoptive transfer of tissue homing, LAM reactive T cells.

## Key facts

- **NIH application ID:** 10682121
- **Project number:** 1R01HL165841-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** I. Caroline Le Poole
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $605,116
- **Award type:** 1
- **Project period:** 2023-06-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10682121

## Citation

> US National Institutes of Health, RePORTER application 10682121, Time to ATTAC: Adoptive Transfer of T cells Against gp100+ Cells to treat LAM (1R01HL165841-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10682121. Licensed CC0.

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