Institute of Biomedical Sciences

Title

Lymphocyte-nanoparticle biohybrids as a combined nanoimmunotherapy for cancer

Poster Number

14

Document Type

Poster

Keywords

nanoimmunotherapy, lymphocyte, nanoparticle, neuroblastoma, immunotherapy

Publication Date

4-2017

Abstract

T cell therapies have shown promise against leukemias, but little efficacy against solid tumors. Success is limited by an immunosuppressive tumor environment, which precludes effector cell accumulation at the tumor site or renders effector cells dysfunctional preventing tumor clearance. As such, strategies to improve effector cell function at the tumor site have the potential to enhance responses. We have observed that multifunctional nanoparticles can confer additional properties to existing cell-based immunotherapies including ablative heating, magnetic responsiveness, and localized drug delivery. We thus sought to evaluate whether immune cell-nanoparticle biohybrids (ImmunoNPs) could combine the potent cytotoxic capabilities of antigen-specific T cells and ablative therapy from nanoparticles to enhance immune responses within the suppressive tumor microenvironment.

We synthesized a robust biohybrid capable of antigen-dependent cytotoxicity, followed by localized ablative therapy to efficiently eliminate residual disease by conjugating T-cells with Prussian blue nanoparticles (which absorb light in the near infrared range). We demonstrated T stable cell-nanoparticle conjugation over at least 3 days (51-65.8% by flow cytometry). T-cells within the biohybrid retained their proliferative ability (66.4% for T-cells vs. 66.5% for biohybrid by CFSE dissolution) and effector phenotype (mean 62.7% CD8+ T-cells vs. 55.2% CD8+ biohybrid, n=7), with no significant increases in markers of exhaustion (PD1, TIM3, LAG3). Furthermore, we demonstrated improved cytotoxicity against tumor antigen-expressing target cells following treatment with ImmunoNPs: each component individually was able to decrease target cell viability from 92.7% (target cells alone) to 46.3% (T-cells alone) or 43.8% (NPs with laser), however maximal eradication occurred with the tandem biohybrid (target cell viability of 28%). Additionally, we found that ablative therapy with non-cellularized Prussian blue nanoparticles was capable of increasing tumor lymphocyte infiltration 3-fold (p<0.05) compared to untreated tumors in vivo, suggesting that photothermal ablation can augment endogenous immune responses.

We believe this work represents a novel modality that combines the strengths of cell-based immunotherapy with nanomedicine in order to achieve maximal therapeutic responses to challenging malignancies and infectious diseases.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

1

Comments

To be presented at GW Annual Research Days 2017.

This document is currently not available here.

Share

COinS
 

Lymphocyte-nanoparticle biohybrids as a combined nanoimmunotherapy for cancer

T cell therapies have shown promise against leukemias, but little efficacy against solid tumors. Success is limited by an immunosuppressive tumor environment, which precludes effector cell accumulation at the tumor site or renders effector cells dysfunctional preventing tumor clearance. As such, strategies to improve effector cell function at the tumor site have the potential to enhance responses. We have observed that multifunctional nanoparticles can confer additional properties to existing cell-based immunotherapies including ablative heating, magnetic responsiveness, and localized drug delivery. We thus sought to evaluate whether immune cell-nanoparticle biohybrids (ImmunoNPs) could combine the potent cytotoxic capabilities of antigen-specific T cells and ablative therapy from nanoparticles to enhance immune responses within the suppressive tumor microenvironment.

We synthesized a robust biohybrid capable of antigen-dependent cytotoxicity, followed by localized ablative therapy to efficiently eliminate residual disease by conjugating T-cells with Prussian blue nanoparticles (which absorb light in the near infrared range). We demonstrated T stable cell-nanoparticle conjugation over at least 3 days (51-65.8% by flow cytometry). T-cells within the biohybrid retained their proliferative ability (66.4% for T-cells vs. 66.5% for biohybrid by CFSE dissolution) and effector phenotype (mean 62.7% CD8+ T-cells vs. 55.2% CD8+ biohybrid, n=7), with no significant increases in markers of exhaustion (PD1, TIM3, LAG3). Furthermore, we demonstrated improved cytotoxicity against tumor antigen-expressing target cells following treatment with ImmunoNPs: each component individually was able to decrease target cell viability from 92.7% (target cells alone) to 46.3% (T-cells alone) or 43.8% (NPs with laser), however maximal eradication occurred with the tandem biohybrid (target cell viability of 28%). Additionally, we found that ablative therapy with non-cellularized Prussian blue nanoparticles was capable of increasing tumor lymphocyte infiltration 3-fold (p<0.05) compared to untreated tumors in vivo, suggesting that photothermal ablation can augment endogenous immune responses.

We believe this work represents a novel modality that combines the strengths of cell-based immunotherapy with nanomedicine in order to achieve maximal therapeutic responses to challenging malignancies and infectious diseases.