Injectable Hydrogels as Local Depots at Tumor Sites for Antitumor Immunotherapy and Immune-Based Combination Therapy

Macromol Biosci. 2021 Jun;21(6):e2100039. doi: 10.1002/mabi.202100039. Epub 2021 Apr 5.

Abstract

Despite the encouraging clinical responses of several human cancers to immunotherapy, the efficacy of this treatment remains limited by variable objective response rates and severe systemic immune-related adverse events. To overcome these issues, injectable hydrogels have been developed as local depots that permit the sustained release of single or multiple immunotherapy agents, including traditional immunomodulatory factors, immune checkpoint blocking antibodies, and exogenous immune cells. The antitumor efficacy of immunotherapy can also be enhanced by its combination with other therapeutic approaches, including chemotherapy, radiotherapy, and phototherapy. Despite local treatment strategies, potent systemic antitumor immune responses with low systemic toxicity can be obtained, leading to significant local and abscopal tumor-killing, reduced tumor metastasis, and the prevention of tumor recurrence. This review highlights recent progress in injectable hydrogel-based local depots for tumor immunotherapy and immune-based combination therapy. Moreover, the proposed mechanisms responsible for these antitumor effects are discussed.

Keywords: combination therapy; immunotherapy; injectable hydrogel; local delivery system; tumor treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology
  • Combined Modality Therapy / methods*
  • Cytokines / pharmacology
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Humans
  • Hydrogels / administration & dosage*
  • Hydrogels / chemistry
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunologic Factors / pharmacology
  • Immunotherapy / methods
  • Induction Chemotherapy / methods
  • Molecular Targeted Therapy / methods
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Phototherapy / methods

Substances

  • Antimetabolites, Antineoplastic
  • Cytokines
  • Hydrogels
  • Immune Checkpoint Inhibitors
  • Immunologic Factors