Immunotherapy against glioblastoma using backpack-activated neutrophils.

in Bioengineering & translational medicine by Tatsuya Fukuta, Ninad Kumbhojkar, Supriya Prakash, Suyog Shaha, A Da Silva-Candal, Kyung Soo Park, Samir Mitragotri

TLDR

  • Researchers develop a novel therapeutic approach using neutrophils with attached drug-free micro-patches (CAMPs) in combination with anti-PD1 antibody to improve the efficacy of immunotherapy against glioblastoma multiforme (GBM).

Abstract

Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug-free disk-shaped backpacks, termed Cyto-Adhesive Micro-Patches (CAMPs) for treating GBM. CAMP-adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti-PD1 antibody (aPD-1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD-1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice-bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD-1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD-1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.

Overview

  • The study investigates the use of neutrophils with attached drug-free disk-shaped backpacks (Cyto-Adhesive Micro-Patches, CAMPs) in combination with anti-PD1 antibody (aPD-1) for treating glioblastoma multiforme (GBM).
  • The study aims to improve the efficacy of Immunotherapy Checkpoint Inhibitors (ICIs) by stimulating local and systemic immune environments using CAMP-adhered neutrophils (NE/CAMPs).
  • The researchers tested the efficacy of NE/CAMPs in combination with aPD-1 in both subcutaneous and orthotopic murine GBM models.

Comparative Analysis & Findings

  • In the subcutaneous murine GBM model, NE/CAMPs significantly improved the efficacy of aPD-1, leading to complete regression of tumors in mice.
  • In the orthotopic GBM model, the combination treatment of NE/CAMPs and aPD-1 showed improved therapeutic responses compared to aPD-1 alone, activating systemic immune responses mediated by T cells.
  • CAMP attachment did not affect the ability of neutrophils to migrate into the brain, and intracerebral NE/CAMP accumulation was observed in mice-bearing orthotopic GBM.

Implications and Future Directions

  • The study suggests that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.
  • Future studies should investigate the combination of NE/CAMPs with other immunotherapy approaches to improve treatment outcomes.
  • The safety and efficacy of NE/CAMPs in human clinical trials should be evaluated to confirm their effectiveness in treating GBM.
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