# A comparative analysis of human and canine iNKT cells for ACT

> **NIH NIH U24** · UNIVERSITY OF PENNSYLVANIA · 2021 · $238,466

## Abstract

PROJECT SUMMARY (See instructions):
 The holy grail of adoptive cell therapies (ACT) is the generation of fit, ready-to-use, CART products from
healthy donors that could be safely and effectively transferred across allogeneic barriers to improve the
availability and efficacy of CAR-therapies. Invariant Natural Killer T cells (iNKT) are a heterogenous population
of `non-conventional' T cells expressing an invariant TCRα which recognizes the non-polymorphic, glycolipid-
presenting MHC molecule CD1d. As such, unedited allogeneic iNKT cells (allo-iNKT) can be adoptively
transferred without causing GVHD. Further, iNKT cells suppress GVHD caused by conventional T cells and
inhibit rejection of allogeneic cells promoting lifelong tolerance of solid organ grafts. In addition, iNKT cells have
natural tumor tropism, kill CD1d+ tumor associated macrophages and activate effector immune cells in the tumor.
Given these properties, we hypothesize that allo-iNKT could be safely and effectively used to promote allo-CART
persistence and enhance anti-tumor immunity.
 The complexity of iNKT function may be attributed to distinct iNKT subsets that exhibit cytotoxic versus
regulatory properties. Understanding subset heterogeneity would enable the most “desirable” iNKT subsets to
be selected for evaluation of combination ACT. Unlike mice, canine iNKT cells share similar phenotypic and
biological features to human iNKT cells, suggesting that pet dogs with spontaneous cancer may represent the
ideal pre-clinical model to investigate combination allo-ACT using iNKT cells. Here, in alignment with the aims
of PRECINCT to support canine immunotherapy clinical trials and generate immunological reagents and with
the interest of IOTN to generate an off-the-shelf CART cell platform, we will perform a comparative approach to
investigate actionable iNKT cell heterogeneity through an integrated, single cell RNAseq/CITEseq approach in
human iNKT and employ transfer learning to impute phenotypic markers of canine iNKT subsets from scRNA
seq data. Furthermore, to expand the immunoreagent toolbox for canine NK studies, a comprehensive scFv
phage display library will be used in simple panning experiments to generate and validate much needed canine-
specific antibodies against NK activation and inhibitory receptors that will be of value in understanding the
mechanisms governing canine NK activation and inhibition. Together, these studies will lay the necessary
groundwork for future generation and in vivo testing of optimal iNKT cell products for combination allo-
iNKT/CART therapies in immune competent canine cancer patients, with the goal to accelerate novel allo-ACT
strategies into the human clinic.
 RELEVANCE (See instructions):
 The natural properties of iNKT cells lend themselves to safe allogeneic adoptive transfer and suppression
of alloreactive responses that would otherwise eliminate allo-CART products. Here, we will provide the
necessary comparative evaluation of human and canin...

## Key facts

- **NIH application ID:** 10287095
- **Project number:** 3U24CA224122-02S2
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Qi Long
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $238,466
- **Award type:** 3
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287095

## Citation

> US National Institutes of Health, RePORTER application 10287095, A comparative analysis of human and canine iNKT cells for ACT (3U24CA224122-02S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10287095. Licensed CC0.

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