# SPORE in Lymphoma

> **NIH NIH P50** · BAYLOR COLLEGE OF MEDICINE · 2020 · $2,179,484

## Abstract

OVERALL PROJECT SUMMARY
The overarching goal of this SPORE renewal proposal is to devise and test novel forms of cellular
immunotherapy mediated by T cells and NKT cells to treat non-Hodgkin lymphoma (NHL) or Hodgkin
lymphoma (HL). A distinguished cadre of molecular biologists, immunologists and clinical investigators with
exemplary histories of productive translational research, and supported by four shared core resources, has
been recruited for this effort. To address the persistent challenges of unsustained complete remissions and
unacceptable rates of treatment-related toxicity, investigators in this program have proposed four distinct
lines of research, each involving an early-phase clinical trial. 1) Use highly specific T and natural killer T
(NKT) cell immunotherapies to target multiple lymphoma antigens. This objective will be pursued in each
project using either native or chimeric antigen receptors (CARs) or both. 2) To increase the potency of the T
and NKT cell immunotherapies for lymphoma. This will entail an immunomodulatory agent, 5-azacytidine, to
increase tumor antigen expression (Project 1); developing CARs for independent targets on T cell lymphoma
(Project 2); adding a nonlytic costimulatory CAR to supply increased “signal-2” elements to improve the
expession and perisistence of EBV-specific T cells (Project 3); and use of a CD19-CAR to enhance tumor
recognition and provide added costimulation (Project 4). 3) Overcome the immune evasion tactics of
lymphoma cells and their microenvironment. Investigators will use a modified inverted cytokine receptor to
interact with immunosuppressive molecules at the tumor site while delivering positive costimulatory signals
(Project 1); will exploit a novel costimulatory CAR to enable T cells to sustain their activation in the presence
of immunosuppressive molecules (Project 3); and will take advantage of the ability of NKT cells to overcome
the immunosuppressive microenviornment to boost response rates (Project 4). 4) Make T and NKT cell
immunotherapy more broadly applicable. Innovations in the manufacturing practices of this SPORE will
continue to improve the technologies required for the success of each project, including further reductions in
the length and complexity of T-cell preparation (Projects 1-3) and use of banked NKT cells as an “off-the-
shelf” product (Project 4). At the conclusion of these proposed studies, we will have evaluated the clinical
feasibility and safety of several novel immunotherapy approaches to NHL and HL, and gained valuable insight
into the immune variables that correlate with clinical outcome after targeted immunotherapy. These
achievements will represent substantive steps toward the development of novel lymphoma treatments that are
both potent and widely accessible.

## Key facts

- **NIH application ID:** 10000834
- **Project number:** 5P50CA126752-14
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** MALCOLM K. BRENNER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,179,484
- **Award type:** 5
- **Project period:** 2007-04-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000834

## Citation

> US National Institutes of Health, RePORTER application 10000834, SPORE in Lymphoma (5P50CA126752-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10000834. Licensed CC0.

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