Quantitative MRI cell tracking of immune cell recruitment to tumors and draining lymph nodes in response to anti-PD-1 and a DPX-based immunotherapy

ABSTRACT

DPX is a unique T cell activating formulation that generates robust immune responses (both clinically and preclinically) which can be tailored to various cancers via the use of tumor-specific antigens and adjuvants. While DPX-based immunotherapies may act complementary with checkpoint inhibitors, combination therapy is not always easily predictable based on individual therapeutic responses. Optimizing these combinations can be improved by understanding the mechanism of action underlying the individual therapies. Magnetic Resonance Imaging (MRI) allows tracking of cells labeled with superparamagnetic iron oxide (SPIO), which can yield valuable information about the localization of crucial immune cell subsets. In this work, we evaluated the use of a multi-echo, single point MRI pulse sequence, TurboSPI, for tracking and quantifying cytotoxic T lymphocytes (CTLs) and myeloid lineage cells (MLCs). In a subcutaneous cervical cancer model (C3) we compared untreated mice to mice treated with either a single therapy (anti-PD-1 or DPX-R9F) or a combination of both therapies. We were able to detect, using TurboSPI, significant increases in CTL recruitment dynamics in response to combination therapy. We also observed differences in MLC recruitment to therapy-draining (DPX-R9F) lymph nodes in response to treatment with DPX-R9F (alone or in combination with anti-PD-1). We demonstrated that the therapies presented herein induced time-varying changes in cell recruitment. This work establishes that these quantitative molecular MRI techniques can be expanded to study a number of cancer and immunotherapy combinations to improve our understanding of longitudinal immunological changes and mechanisms of action.

KEYWORDS:

• magnetic resonance imaging (MRI)
• immunotherapy
• anti-PD-1
• cytotoxic T lymphocytes (CTLs)
• myeloid lineage cells (MLCs)

Acknowledgments

The authors would like to thank Caitrin Sobey-Skelton for help with text, data analysis, and with some biological assays. We would also like to thank Raj Rajagopalan for assistance in preparing the DPX-based immunotherapies.

Disclosure statement

At the time of writing this manuscript, MLT, GW, and MS were employees of IMV Inc., who manufactures DPX-based immunotherapies. KDB also had a research contract with IMV for an unrelated project.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

KDB would like to acknowledge that this work was funded by the Nova Scotia Health Research Foundation (NSHRF) in the form of an establishment grant and the National Sciences and Engineering Research Council (NSERC) in the form of a Discovery grant. WMK would like to acknowledge funding from the NIH; R01 CA74397.