T cells as antigen carriers for anti-tumor vaccination

Catia Traversari, Vincenzo Russo

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The exploitation of the physiologic processing and presenting machinery of dendritic cells (DCs) by in vivo loading of tumor-associated antigens may improve the immunogenic potential and clinical efficacy of DC-based cancer vaccines. The approach developed by our group was based on the clinical observation that some patients treated with the infusion of donor lymphocytes transduced to express the HSV-TK suicide gene for relapse of hematologic malignancies, after allogeneic hematopoietic stem cell transplantation, developed a T cell-mediated immune response specifically directed against the HSV-TK gene product. We demonstrated that lymphocytes genetically modified to express HSV-TK as well as self/tumor antigens, acting as antigen carriers, efficiently target DCs in vivo in tumor-bearing mice. The infusion of TRP-2-transduced lymphocytes induced the establishment of protective immunity and long-term memory in tumor-bearing mice by cross-presentation of the antigen mediated by the CD11c + CD8a + DCs subset. A similar approach was applied in a clinical setting. Ten patients affected by MAGE-3 + metastatic melanoma were treated with autologous lymphocytes retrovirally transduced to express the MAGE-3 tumor antigen. In three patients, the treatment led to the increase of MAGE-3 specific CD8+ and CD4+ effectors and the development of long-term memory, which ultimately correlated with a favorable clinical outcome. Transduced lymphocytes represent an efficient way for in vivo loading of tumor-associated antigens of DCs.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages97-104
Number of pages8
Volume1393
DOIs
Publication statusPublished - Apr 1 2016

Publication series

NameMethods in Molecular Biology
Volume1393
ISSN (Print)10643745

Keywords

  • Active immunotherapy
  • Cross-presentation
  • Tumor antigens

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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