# Immunotherapy of B cell lymphoma with  NK-T cells

> **NIH NIH P50** · BAYLOR COLLEGE OF MEDICINE · 2021 · $248,724

## Abstract

PROJECT SUMMARY
T cells expressing CD19-specific chimeric antigen receptors (CAR.CD19) can produce high rates of
complete remission among patients with refractory B-cell malignancies. However, these studies have also
revealed (i) difficulties in preparing sufficient numbers of CAR-T cells from the majority of pediatric patients
with non-Hodgkin lymphoma (NHL), and (ii) a growing fraction of NHL patients with delayed relapse due to
inadequate persistence of CAR-T cells or loss of CD19 from tumor cells. The long-term goal of Project 4 is
to develop a safe and effective immunotherapy for NHL using both the natural and engineered properties of
CD1d-restricted Va24-invariant natural killer T (NKT) cells. NKTs are attractive candidates for
immunotherapy. They have antilymphoma activity via direct cytotoxicity against CD1d+ lymphoblasts or by
activation of other immune effectors, such as NK cells; further, allogeneic NKTs do not produce graft-
versus-host disease (GvHD) and can be prepared as “off-the-shelf” products. We hypothesize that
allogeneic NKTs engineered to express CAR.CD19 will show curative potential against NHL without the
introduction of GvHD, a concept supported by our preliminary findings: NKTs transduced with CAR.CD19
directly kill CD19+ B lymphoblasts, can be expanded to clinical scale, and exert potent antitumor activity in
xenogeneic lymphoma models. We have also shown that the CD62L+ subset of NKTs is essential for
CAR.CD19-Tcell persistence and antitumor activity in vivo, and have devised means to preserve this subset
of cells during CAR.CD19-NKT expansion. The following three specific aims will test our hypothesis: 1)
Generate allogeneic CAR.CD19-NKTs with preserved CD62L expression and maximal antilymphoma
potential, using the costimulatory aAPCs (artificial antigen-presenting cells, previously generated during the
current funding period). 2) Determine the safety and antitumor activity of third-party CAR.CD19-NKTs in
adult and pediatric patients with relapsed/refractory B-cell NHL. 3) Correlate the persistence, phenotype
and function of CAR.CD19-NKTs with clinical responses. This study will the first in man to test the
feasibility and therapeutic potential of immunotherapy with CAR-redirected NKTs. Our emphasis on
CAR.CD19, with its favorable track record when expressed by T cells in NHL patients, will allow us to
assess NKTs as a novel platform for NHL immunotherapy and perhaps other types of cancer as well.

## Key facts

- **NIH application ID:** 10247742
- **Project number:** 5P50CA126752-15
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Leonid S Metelitsa
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $248,724
- **Award type:** 5
- **Project period:** 2007-04-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247742

## Citation

> US National Institutes of Health, RePORTER application 10247742, Immunotherapy of B cell lymphoma with  NK-T cells (5P50CA126752-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247742. Licensed CC0.

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