Checkpoint blockade and nanosonosensitizer-augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice

Nat Commun. 2019 May 2;10(1):2025. doi: 10.1038/s41467-019-09760-3.

Abstract

Combined checkpoint blockade (e.g., PD1/PD-L1) with traditional clinical therapies can be hampered by side effects and low tumour-therapeutic outcome, hindering broad clinical translation. Here we report a combined tumour-therapeutic modality based on integrating nanosonosensitizers-augmented noninvasive sonodynamic therapy (SDT) with checkpoint-blockade immunotherapy. All components of the nanosonosensitizers (HMME/R837@Lip) are clinically approved, wherein liposomes act as carriers to co-encapsulate sonosensitizers (hematoporphyrin monomethyl ether (HMME)) and immune adjuvant (imiquimod (R837)). Using multiple tumour models, we demonstrate that combining nanosonosensitizers-augmented SDT with anti-PD-L1 induces an anti-tumour response, which not only arrests primary tumour progression, but also prevents lung metastasis. Furthermore, the combined treatment strategy offers a long-term immunological memory function, which can protect against tumour rechallenge after elimination of the initial tumours. Therefore, this work represents a proof-of-concept combinatorial tumour therapeutics based on noninvasive tumours-therapeutic modality with immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • Cell Line, Tumor / transplantation
  • Combined Modality Therapy / methods
  • Disease Models, Animal
  • Drug Screening Assays, Antitumor
  • Female
  • Hematoporphyrins / administration & dosage
  • Humans
  • Imiquimod / administration & dosage
  • Immunotherapy / methods*
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Neoplasm Metastasis / immunology
  • Neoplasm Metastasis / therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Treatment Outcome
  • Ultrasonic Therapy / methods*

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Hematoporphyrins
  • Liposomes
  • hematoporphyrin monomethyl ether
  • Imiquimod