Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Engineering Chimeric Ligand Presenting T Cells (CLiP-Ts) Targeting Receptors of Extranodal NK/T-Cell Lymphoma: A Comparative Study with Traditional CAR-T Cell Therapy

Award Number: F30CA310065
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2026
PERIOD OF PERFORMANCE END DATE: 11/30/2027

Group Awards By:

View Award Description

Engineering Chimeric Ligand Presenting T Cells (CLiP-Ts) Targeting Receptors of Extranodal NK/T-Cell Lymphoma: A Comparative Study with Traditional CAR-T Cell Therapy - Project Summary Extranodal NK/T cell lymphoma (ENKTL) is a rare, aggressive subtype of non-Hodgkin’s lymphoma (NHL). It is characterized by extra-nodal tumor growth, particularly in the nasal cavity, skin, and gastrointestinal tract. ENKTL accounts for up to 15% of new lymphoma cases in specific populations. A majority (85%) of ENKTL cases originate from natural killer (NK) cells. ENKTL remains a therapeutic challenge, with advanced or refractory cases carrying a five-year survival rate < 30%. While chimeric antigen receptor T cell (CAR-T) therapy has revolutionized treatment of relapsed or refractory B-cell NHL, no cellular therapy has been developed specifically for ENKTL. The overall objective of this project is to develop a novel class of chimeric ligand-presenting (CLiP) T cells for ENKTL treatment. Each CLiP-T cell expresses a stress-induced ligand, HLA-E or MICA, on its surface to bind ENKTL-specific receptors, NKG2A or NKG2D, respectively. Concurrently, conventional CAR-T cells with a single-chain variable fragment (scFv) against NKG2A or NKG2D were created for comparison in all functional studies. The central novel hypothesis is that CLiP-T cells leveraging ligand-receptor interactions are more effective in treating ENKTL than receptor-receptor interactions of scFvs in CAR-T cells. The rationale is that the ligand-based approach leverages the innate ability of endogenous proteins to bind tightly to their target receptors, thereby directing the antitumor activity of the CLiP-T cell while simultaneously triggering the target receptor’s biological effects, creating a synergistic interaction. The central hypothesis will be tested through two specific aims: 1) Characterization and refinement of HLA-E CLiP-T, MICA CLiP-T, anti-NKG2A CAR-T, and anti- NKG2D CAR-T in vitro, and 2) Compare in vivo tolerability, persistence, and efficacy against ENKTL tumors—HLA-E CLiP-T vs. anti-NKG2A CAR-T and MICA CLiP-T vs. anti-NKG2D CAR-T. The goal of Aim 1 is to understand the biology of CLiP-T cells in comparison to CAR-T cells and to refine three supplementary design components. Aim 2 focuses on comparing the functionality of the CLiP-T and CAR-T cells in vivo. Rigorous, reproducible preliminary data support this novel hypothesis-driven proposal: we validated all CLiP-T and CAR-T constructs and demonstrated that CLiP-T cells eliminate NK92 cells in vitro more effectively than their CAR-T counterparts. The expected outcomes of this proposal include the development of two ligand- based CLiP-T cells expressing HLA-E or MICA as potential disease-specific cellular therapies for ENKTL. These studies are significant because they will establish a first-in-class, disease-specific cellular therapy for ENKTL, provide key insights into NK-cell immune regulation, and offer the first true comparison of ligand- and scFv-based CAR-T approaches. These innovative studies evaluate multiple previously untargeted receptors for cellular therapy and will be the first application of stress-induced proteins to direct CAR-T cell antitumor activity. This work has broad applicability; CLiP-T technology allow virtually any receptor to be targeted therapeutically. This proposal offers exceptional training in the design, construction, and evaluation of cellular therapies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $55,114 )
2026	2026	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Cancer Research Manpower	000	1	5/7/2026	NEW	$55,114
														Subtotal = $55,114

Grand Total All Awards = $55,114

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Engineering Chimeric Ligand Presenting T Cells (CLiP-Ts) Targeting Receptors of Extranodal NK/T-Cell Lymphoma: A Comparative Study with Traditional CAR-T Cell Therapy

Award Number: F30CA310065

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2026

PERIOD OF PERFORMANCE END DATE: 11/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer