Prospects for personalized combination immunotherapy for solid tumors based on adoptive cell therapies and immune checkpoint blockade therapies

Daiki Kato, Tomonori Yaguchi, Takashi Iwata, Kenji Morii, Takayuki Nakagawa, Ryohei Nishimura, Yutaka Kawakami

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors. However, gene-engineered T cells possess strong killing activity and cytokine production capacity, which can induce antigen spreading and modulate the TME of non-T cell-inflamed tumors seen in non-responders to ICB therapy. Immune responses against cancer are highly heterogeneous, not only between tumor types, but also within a patient or between different patients with the same type of cancer, indicating that personalized immunotherapy should be employed, based on the immune status of the individual patient. Here, we offer our perspective for personalized combination immunotherapy for solid tumors based on ACT and ICB therapies.

Original languageEnglish
Pages (from-to)68-77
Number of pages10
JournalJapanese Journal of Clinical Immunology
Volume40
Issue number1
DOIs
Publication statusPublished - 2017

Keywords

  • Adoptive cell therapy
  • Chimeric antigen receptor transduced T (CAR-T) cell therapy
  • Immune checkpoint blockade therapy
  • Tumor immunology
  • Tumor microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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