DC-CTL targeting carbonic anhydrase IX gene combined with iAPA therapy in the treatment of renal cell carcinoma

Hum Vaccin Immunother. 2021 Nov 2;17(11):4363-4373. doi: 10.1080/21645515.2021.1955610. Epub 2021 Dec 1.

Abstract

Introduction: To deliver specific antigens in tumor immunotherapy, tumor cell lysates are commonly used to sensitize dendritic cells (DCs). However, the lysates possess low immunogenicity and contain many types of non-tumor-related antigens, which may induce autoimmune diseases. Tumor antigen peptides can provide high specificity but are expensive and their short half-lives limit their clinical application.

Methods: In this study, we used adenovirus to transfer the carbonic anhydrase IX (CA9) gene into DCs to generate specificity to renal cell carcinoma (RCC) which is the most common space-occupying lesion in humans. Inhibition of antigen presentation attenuators (iAPA) technology was also used to enhance the DC delivery capacity. Finally, DCs were co-cultured with cytotoxic T-lymphocytes (CTLs) and the anti-tumor effects were evaluated.

Results: The results showed that the CA9-DC-CTLs possessed a high specificity to CA9-positive cells and showed stronger anti-tumor activity than GFP-DC-CTLs both in vitro and in vivo.

Discussion: These findings may suggest a novel treatment option for RCC.

Keywords: CA9; DC-CTL; RCC; SOCS1; iAPA; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Antigens, Neoplasm* / genetics
  • Carbonic Anhydrase IX* / genetics
  • Carbonic Anhydrases* / genetics
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / therapy
  • Dendritic Cells*
  • Humans
  • Immunotherapy, Adoptive
  • Kidney Neoplasms* / therapy
  • T-Lymphocytes, Cytotoxic

Substances

  • Antigens, Neoplasm
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases

Grants and funding

This study was supported by Shandong Yinfeng Life Science Research Institute, Shandong Cell-Tissue Bank, and First Affiliated Hospital of Shandong First Medical University (Jinan, China). This study was supported by grant from Department of Science and Technology of Shandong province [grant no.2016ZDJS07B05].