# City of Hope Lymphoma SPORE

> **NIH NIH P50** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2022 · $2,307,384

## Abstract

The overall goal of the City of Hope Lymphoma SPORE is to develop novel therapeutics and prognostics
representing the forefront of knowledge gained from observations in molecular biology and cellular immunology
at City of Hope. Six clinical trials are proposed, five of which utilize agents (cellular products, small molecules,
radiolabeled antibodies) that have been produced at City of Hope and are developed from our preclinical
laboratory studies. In Project 1, we have engineered bi-specific chimeric antigen receptor (CAR) T cells that
respond to both lymphoma antigen and cytomegalovirus (CMV) antigen. Combining bi-specific CAR T cells
with a CMV vaccine developed at City of Hope may enhance CAR T cell persistence and allow in vivo control
of T cells in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) in three clinical settings:
1) lymphodepleting chemotherapy, 2) autologous (auto) hematopoietic cell transplantation (HCT), and
3) allogeneic HCT. Project 2 builds on our previous observations in a prospective longitudinal study of
lymphoma patients undergoing auto HCT, revealing pathogenic mutations contributing to a predictive 38-gene
signature of susceptibility to tMDS/AML. We will now use this City of Hope cohort and an external validation
cohort to develop a comprehensive risk prediction model for developing t-MDS/AML after auto HCT. Project 3
addresses the poor outcomes for patients with relapsed Hodgkin lymphoma with two phase II clinical trials: a
PET-adapted strategy using PD-1 inhibitor nivolumab ± ICE chemotherapy as a bridge to autologous HCT, and
aTac-BEAM, a radioimmunotherapy-based augmented autologous HCT regimen. In Project 4, we propose a
clinical trial of a novel agent linking a CpG oligonucleotide with anti-sense STAT3 siRNA to target NHL and
associated immune cells. We are also developing a modified high-affinity STAT3-DNA binding sequence linked
to a CpG oligonucleotide that inhibits STAT3 by acting as DNA decoy. The SPORE, also supports a Career
Enhancement Program for researchers new to lymphoma research, as well as a Developmental Research
Program for scientists with promising pilot projects. SPORE cores provide crucial support to the success of the
projects: The Administrative Core (Core A) provides organizational and programmatic support; the
Biostatistics and Research Informatics Core (Core B) imparts comprehensive statistical and information
management expertise; and Biospecimen Core (Core C) supports projects as they relate to sample
collection, processing, storage and distribution. The GMP Manufacturing Core (Core D) is responsible for
process development, regulatory support, and cGMP-compliant clinical grade production of novel
investigational agents; this core is an invaluable resource allowing us to rapidly translate laboratory discoveries
to the clinic. Lastly, with a richly diverse catchment area, City of Hope has made a coordinated effort to engage
patients that have been traditionally underrepresente...

## Key facts

- **NIH application ID:** 10456955
- **Project number:** 5P50CA107399-15
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Stephen J Forman
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,307,384
- **Award type:** 5
- **Project period:** 2004-09-02 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456955

## Citation

> US National Institutes of Health, RePORTER application 10456955, City of Hope Lymphoma SPORE (5P50CA107399-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10456955. Licensed CC0.

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