Enhanced systemic antilymphoma immune response by photothermal therapy with CpG deoxynucleotide–coated nanoparticles

Author:

Lin Adam Yuh12ORCID,Choi Bongseo3,Sim Taehoon3,Yang Eva1,Choi Hyunjun3,Behdad Amir24ORCID,Kim Dong-Hyun235ORCID,Gordon Leo I.12ORCID

Affiliation:

1. 1Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL;

2. 2Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL;

3. 3Department of Radiology, and

4. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL; and

5. 5Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL

Abstract

Abstract In preclinical studies, we investigated a novel mechanism of in situ vaccination in lymphoma. Radiation therapy (RT) can induce abscopal responses in lymphoma models, but this has not translated into clinical efficacy. We hypothesized that immune stimulation with cytosine guanine dinucleotide (CpG) deoxynucleotides could enhance abscopal effects induced by RT or photothermal therapy (PTT), which has been shown to have an immune stimulatory effect in solid tumors but has not been studied in lymphoma. We designed a branched gold nanoparticle (NP) platform to carry CpG deoxynucleotides while maintaining PTT function and compared the immunologic profile of the tumor microenvironment after PTT or RT in a dual-flank lymphoma model. One flank was treated with CpG deoxynucleotides with RT or PTT, and the other tumor was left untreated. We found that the CpG deoxynucleotide/PTT group had significant reduction in growth in both treated (primary) and untreated (secondary) tumors, suggesting an improved abscopal response, with a concomitant increase in CD8/CD4 and cytotoxic T-cell/regulatory T-cell ratios in both primary and secondary tumors compared with CpG deoxynucleotides/RT. Dendritic cells in primary and secondary draining lymph nodes had increased maturation markers in the CpG deoxynucleotide/PTT group, and the effector memory T cells (both CD4 and CD8) in the secondary tumor and spleen were increased, suggesting a systemic vaccination effect. These data suggest that in a lymphoma model, PTT using a CpG deoxynucleotide NP platform resulted in enhanced in situ vaccination and abscopal response compared with RT.

Publisher

American Society of Hematology

Subject

Hematology

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