# Aak1 to increase infiltration of adoptively transferred cells into solid tumors

> **NIH NIH R37** · MAYO CLINIC ROCHESTER · 2024 · $434,754

## Abstract

PROJECT SUMMARY/ABSTRACT
Insufficient T cell infiltration is a major challenge in adoptive transfer therapies like CAR-T. Therefore, one
strategy to improve therapy is to enhance T cell trafficking into tumors. However, current therapies targeting T
cell activities largely consist of immune checkpoint modulators, and very little innovation has occurred in
therapeutic design targeting T cell intrinsic regulators of intratumoral accumulation. This is due, in part, to an
incomplete understanding of the regulatory pathways involved in T cell trafficking. We recently identified Adapter
protein 2 associated kinase 1 (Aak1) as an important regulator of T cell chemotaxis into tumors in an in vivo
forward genetic screen. The primary objective of this project is to measure the translational potential of AAK1 as
a therapeutic target in cancer to augment adoptive transfer therapies, with the additional goal of better
understanding molecular functions of Aak1 as a regulator of chemokine receptor Cxcr3 internalization. These
goals will be accomplished in three aims. Aim 1 will quantify the impact of genetic modification of Aak1 on tumor
infiltration of adoptively transferred T cells in a preclinical solid tumor model. Aim 2 will determine whether Aak1
kinase activity is required for chemokine-induced internalization of Cxcr3 in primary T cells. Aim 3 will measure
the degree to which Aak1 modification impacts therapeutic efficacy in adoptive transfer therapies. This proposal
has several innovative aspects, including characterization of a novel, T cell specific Aak1 knockout mouse,
functional and mechanistic testing of a novel Aak1 mutant construct, and evaluation of Aak1 as a novel
therapeutic target to limit T cell chemotaxis into inflamed tissue. Successful completion of this project will benefit
development of novel treatment strategies for solid tumors, and findings can broadly be applied to any T cell
adoptive transfer approach and is not limited to individual CAR or TCR engineered platforms.

## Key facts

- **NIH application ID:** 10789871
- **Project number:** 5R37CA276005-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Laura Marie Rogers
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $434,754
- **Award type:** 5
- **Project period:** 2023-02-16 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10789871

## Citation

> US National Institutes of Health, RePORTER application 10789871, Aak1 to increase infiltration of adoptively transferred cells into solid tumors (5R37CA276005-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10789871. Licensed CC0.

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