# Super Natural Killer Cells That Target Metastases in the Tumor-Draining Lymph Nodes

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2021 · $409,817

## Abstract

Project Summary/Abstract
Tumor-draining lymph nodes (LN) are the first site of metastasis in most types of cancer. The extent of metastasis
in the LN is often used in staging cancer progression. Notably, in recent work the applicants described novel
nanoscale TRAIL-coated liposomes that when conjugated to human natural killer (NK) cells enhance their
endogenous therapeutic potential in killing cancer cells both in vitro and in vivo. In this proof-of-concept study,
the applicants will target these liposomes to the LN by conjugating them to NK cells, and will investigate their
ability to prevent the lymphatic spread of colon cancer tumors in mice. It will be shown that targeting NK cells
with TRAIL liposomes can enhance liposome retention time within regional lymph nodes to induce apoptosis in
cancer cells. If successful, the proposed approach could be used to kill cancer cells within the tumor draining LN
to prevent the lymphatic spread of cancer. The proposed work is organized into three Specific Aims. Specific
Aim 1: To examine the mechanism of TRAIL/Anti-NK1.1 liposome therapy and test their efficacy against drug-
resistant colon carcinoma in a subcutaneous LN metastasis model. Sub-aim 1.1: Examine the roles of different
natural killer cell receptors on super NK cytotoxicity. Sub-aim 1.2: To test the efficacy of TRAIL/Anti-NK1.1
liposomes to treat oxaliplatin-resistant colon cancer. Oxaliplatin is a clinically important platinum-based drug
however long-term treatments with oxaliplatin have been shown to lead to the acquisition of drug resistance in
colorectal cancer cells. Specific Aim 2: To characterize the biodistribution, pharmacokinetics and toxicity of
TRAIL/Anti-NK1.1 liposomes introduced intraperitoneally. Intraperitoneal route of liposome injection will be
examined to enable efficacy studies in the orthotopic colon cancer model of Aim 3. Sub-aim 2.1: To examine
the whole body biodistribution and LN pharmacokinetics of TRAIL/Anti-NK1.1 liposomes, with special focus on
the mesenteric lymph nodes. Sub-aim 2.2: To assess for toxicity in response to repeated intraperitoneal
injections of TRAIL/Anti-NK1.1 liposomes. Specific Aim 3: To evaluate TRAIL/Anti-NK1.1 liposome efficacy in an
orthotopic model of colon cancer metastasis to the mesenteric lymph nodes and spleen-to-liver metastasis. Sub-
aim 3.1: Characterize the efficacy of TRAIL/Anti-NK1.1 liposomes to treat orthotopic colon cancer metastasis to
the mesenteric lymph nodes. Sub-aim 3.2:Treatment of secondary metastasis from the spleen to the liver with
intravenous TRAIL/Anti-NK1.1 liposomes. Colon carcinoma cells will be injected into the spleen, a lymphatic
organ, to examine whether intravenous TRAIL/Anti-NK1.1 liposome treatment can also prevent or reduce
secondary metastasis from the spleen to the liver. IMPACT: This innovative TRAIL-liposome based intervention
will demonstrate that NK cells can be used to eliminate tumorigenic cells in the tumor-draining LN, and thus
prevent the for...

## Key facts

- **NIH application ID:** 10057356
- **Project number:** 5R01CA203991-06
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Michael R. King
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $409,817
- **Award type:** 5
- **Project period:** 2016-12-23 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057356

## Citation

> US National Institutes of Health, RePORTER application 10057356, Super Natural Killer Cells That Target Metastases in the Tumor-Draining Lymph Nodes (5R01CA203991-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10057356. Licensed CC0.

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