Antibody-Conjugated Nanogel with Two Immune Checkpoint Inhibitors for Enhanced Cancer Immunotherapy

Yun Jin Chae, Kang Gon Lee, Doogie Oh, Su Kyoung Lee, Yongdoo Park, Jongseong Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer immunotherapy by immune checkpoint inhibitors (ICIs) acts on antitumor responses by stimulating the immune system to attack cancer cells. However, this powerful therapy is hampered by its high treatment cost and limited efficacy. Here, it is shown that the development of an antibody-conjugated nanogel (ANGel), consisting of N-isopropylacrylamide-co-acrylic acid and antibody-binding protein (protein A), potentiates the efficacy of two ICI monoclonal antibodies (mAbs) (cytotoxic-T-lymphocyte-associated antigen 4 and programmed death ligand-1 mAbs). Compared with mAb treatment alone, treatment with a bispecific ANGel surface-conjugated with the mAbs significantly decreases both the survival of Michigan Cancer Foundation-7 (MCF-7) and M D Anderson-Metastatic Breast-231 (MDA-MB-231) breast cancer cells in vitro and the burden of 4T1-luciferase-2-derived orthotopic syngeneic tumors in vivo. The bispecific ANGel is also more potent than the conventional treatment at prolonging survival in animals with triple-negative breast cancer. The advantage of the bispecific ANGel over other engineered bispecific antibodies arises not only from the adaptability to link multiple antibodies quickly and easily, but also from the capability to maintain the anticancer effect steadily at subcutaneously delivered tumor site. This finding has an important implication for cancer immunotherapy, opening a new paradigm to treat solid tumors.

Original languageEnglish
JournalAdvanced Healthcare Materials
DOIs
Publication statusAccepted/In press - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.

Keywords

  • cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4)
  • deformable nanogels
  • programmed death ligand-1 (PD-L1)
  • solid tumors
  • triple negative breast cancer

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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