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

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.

• Authors: Heran Ma, Yi Tan, Dingke Wen, Na Qu, Qunfang Kong, Kun Li, Suxia Ma, Jianhui Zhang
• Journal: Human vaccines & immunotherapeutics (Hum Vaccin Immunother) Vol. 17 Issue 11 Pg. 4363-4373 (11 02 2021) ISSN: 2164-554X [Electronic] United States
• PMID: 34851805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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