# Engineering Precision Medicine to Enhance Graft-Versus-Lymphoma Effect

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $183,924

## Abstract

Project Summary/Abstract
Dr. Satiro De Oliveira, M.D. is an Assistant Professor of Pediatrics in the Division of Hematology/Oncology at
UCLA with research interests in biology of transplantation and cancer immunotherapy. His long-term goals are
to bring cellular therapy approaches to standard clinical practice. His mentor, Dr. Donald Kohn, M.D., is highly
qualified and internationally recognized gene therapy exponent and mentor. A Scientific Advisory Committee has
been assembled to combine excellent mentorship skills and expertise in cancer immunotherapy and non-
Hodgkin lymphoma to provide guidance for the career development and research plan.
Non-Hodgkin lymphomas (NHL) are the fifth most prevalent cancer in the US; patients with refractory or recurrent
NHL have less than 50% of chance of cure. The main goal of this proposal is to use gene modification of
hematopoietic stem cells (HSC) with chimeric antigen receptors (CAR) targeting CD19, a molecule present in
the majority of the NHL. CAR are synthetic chimeric proteins composed of the antigen-recognition portion of a
monoclonal antibody fused to intracellular signaling domains able to activate immune cells. CAR-modification of
HSC brings the prospect of long-term persistence and CAR expression in multiple hematopoietic lineages,
amplifying graft-versus-lymphoma activity; CAR+ HSC could be infused in the context of standard autologous
hematopoietic stem cell transplantation.
A robust in vivo model of humanized NSG mice engrafted with anti-CD19-CAR-modified HSC has been recently
published by Dr. De Oliveira. Detailed evaluation of this approach will lead to a first-in-human clinical trial. A key
feature of this K23 application is the use of paired samples of HSC and NHL tumors from patients, with correlation
to their demographics, expression of membrane proteins on tumor cells, clinical data and therapeutic outcomes.
The scientific questions addressed in this proposal are:
Aim 1. Will CAR-modified HSC lead to lasting immunological memory and persistent anti-cancer activity?
1.1. Comparative evaluation of CD28 and 4-1BB co-stimulatory molecules in the anti-CD19 CAR constructs used
for modification of human HSC.
1.2. Evaluation of anti-CD19 activity in mice engrafted with CAR-modified human HSC at multiple time-points
and after serial tumor challenges.
1.3. Evaluation of the generation of memory T cell subsets from CAR-modified human HSC in mice compared
to adoptively transferred CAR-modified human T cells.
Aim 2. How robust is the protection of CAR-modified HSC against CD19+ NHL primary tumors?
2.1. Evaluation of humanization of NSG mice with gene-modified HSC from B cell NHL patients.
2.2. Characterization of the phenotype of primary NHL tumor cells using mass cytometry (CyTOF).
2.3. Evaluation of anti-lymphoma activity in humanized mice challenged with primary B cell NHL tumors.

## Key facts

- **NIH application ID:** 10352201
- **Project number:** 5K23CA222659-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** SATIRO NAKAMURA DE OLIVEIRA
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $183,924
- **Award type:** 5
- **Project period:** 2017-09-18 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352201

## Citation

> US National Institutes of Health, RePORTER application 10352201, Engineering Precision Medicine to Enhance Graft-Versus-Lymphoma Effect (5K23CA222659-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10352201. Licensed CC0.

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