# PD-1 blockade with cryoablation and dendritic vaccine to treat lymphoma

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2022 · $485,760

## Abstract

The primary object of this proposal is to conduct a Phase II clinical trial testing a novel immunotherapy
combination with programmed death protein 1 (PD-1) blockade, cryoablation, and intra-tumor injection of
dendritic cell vaccines (DC) in non-Hodgkin lymphoma (NHL). NHL is the seventh most common type of cancer
and one of the top ten causes of cancer deaths in United States. Patients with aggressive NHL continue to
have poor survival with salvage treatments at the time of relapsed or refractory disease. Indolent NHL remains
incurable, making less toxic but effective treatment an important part of therapy selection consideration. For
both these considerations, immunotherapy has been one of the most exciting advances in the recent years.
We have completed a Phase I study treating NHL patients with cryoablation and intra-tumor injections of
autologous DC into the cryoablated tumors. This treatment was very well tolerated with no major adverse
events. More importantly, abscopal systemic response was seen with this non-toxic, localized immunotherapy
approach. Five of the 10 treated patients had partial response with an average time to progression of 64 weeks
(range 51-80 weeks). Building on this promising approach, we have identified two deficiencies that can be
targeted with PD-1 blockade: 1. DCs have increased PD-L1 (programmed death ligand-1) expressions that
impairs their ability to prime CD8 T cell for antigen-specific responses; 2. Increased presence of a novel
population of tumor-reactive CD8 T cells in the blood and tumors of lymphoma patients with decreased effector
functions and capacity to differentiate into memory cells. We hypothesize that the combination of PD-1
blockade with monoclonal antibody Pembrolizumab (supplied by Merck), cryoablation and intra-tumor DC
therapy will improve clinical efficacy through improved anti-lymphoma immunity through a combination of
increased antigenic response, increased effector function and or decreased immunosuppressive phenotype.
We have designed a Phase I/II study and secured funding for the Phase I portion of the study where the MTD
of this combination will be determined. In this proposed study, we aim to complete the phase II portion of the
study to determine the clinical efficacy and examine the immunity changes with this novel combination
immunotherapy in NHL.

## Key facts

- **NIH application ID:** 10453752
- **Project number:** 5R01CA219960-06
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Yi Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $485,760
- **Award type:** 5
- **Project period:** 2017-08-02 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453752

## Citation

> US National Institutes of Health, RePORTER application 10453752, PD-1 blockade with cryoablation and dendritic vaccine to treat lymphoma (5R01CA219960-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10453752. Licensed CC0.

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