# Project 2: Microenvironment Modification and Anti-PD1 Immunotherapy of Lymphoma

> **NIH NIH P50** · UNIVERSITY OF IOWA · 2021 · $245,601

## Abstract

ABSTRACT: Project 2. There have been major advances in recent years enhancing our understanding of the
immune response to cancer in general and lymphoma in particular. These advances have impacted on clinical
care. The SPORE has a long-standing interest in exploring the unique aspects of the lymphoma
microenvironment and how cross-talk between malignant lymphocytes and benign cells contributes to both
tumor growth and immunosuppression. SPORE investigators have also explored novel approaches to
modifying that microenvironment in a way that enhances antigen presentation and development of an anti-
lymphoma T cell response. T-cell checkpoint blockade is creating great excitement in the overall field of cancer
immunotherapy but early phase studies indicate it has suboptimal efficacy as a single agent in non-Hodgkin
lymphoma (NHL). Based on this background, the underlying hypothesis of Project 2 is that modifying the
lymphoma microenvironment to augment antigen release, uptake and presentation, will increase the lymphoma
T cell response and enhance the efficacy anti-PD1 therapy of NHL. We will assess this hypothesis by exploring
two specific aims. In the first aim, we will conduct parallel clinical trials combining anti-PD1 therapy with in situ
immunization based on intratumoral manipulation of the NHL microenvironment using two distinct strategies.
The first strategy involves enhancing antigen release and uptake through node cryoablation followed by
intratumoral injection of autologous dendritic cells (DCs). The second strategy involves enhancing antigen
presentation and T cell activation through intratumoral injection of virus-like particles (VLPs) containing a Toll
Like Receptor 9 (TLR9) agonist. In the second aim, we will evaluate the immune response to these treatments,
with a focus on the systemic and intratumoral T cell response. Additional clinical and correlative studies will be
designed based on lessons learned from the first set of clinical trials and correlative science. Overall, this
project will provide critical information on whether local modification of the microenvironment can enhance the
overall systemic immune response and therapeutic efficacy of anti-PD1 therapy, and what approach is best to
achieve that goal.

## Key facts

- **NIH application ID:** 10208778
- **Project number:** 5P50CA097274-20
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** George J. Weiner
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $245,601
- **Award type:** 5
- **Project period:** 2002-09-11 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208778

## Citation

> US National Institutes of Health, RePORTER application 10208778, Project 2: Microenvironment Modification and Anti-PD1 Immunotherapy of Lymphoma (5P50CA097274-20). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10208778. Licensed CC0.

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