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Taking lessons from dendritic cells: multiple xenogeneic ligands for leukocyte integrins have the potential to stimulate anti-tumor immunity

Version 2 2024-06-13, 10:45
Version 1 2017-07-27, 11:37
journal contribution
posted on 2024-06-13, 10:45 authored by JR Kanwar, RW Berg, K Lehnert, GW Krissansen
Expression of large numbers of different costimulatory integrin ligands (CILs) attributes dendritic cells with an ability to induce primary anti-tumor immune responses. Here, we show that optimized gene transfer of the xenogeneic (human) CILs VCAM-1, MAdCAM-1 and ICAM-1 causes rapid and complete rejection of established mouse EL-4 tumors, and generates prolonged systemic anti-tumor immunity; whereas human E-cadherin weakly slows tumor growth. In each case the immune response was mediated by CD8+ T cells and NK cells, accompanied by augmented tumor-specific cytolytic T cell (CTL) activity involving both the perforin and Fas-ligand pathways. Adoptive transfer of splenocytes from cured mice rapidly cleared established tumors in recipients. The mechanism for CIL-mediated immunity is unknown, but may involve CTL-facilitated tumor lysis, since CTLs were generally twice as efficient at killing CIL-transfected tumor cells than parental tumor cells. Optimized CIL-based gene therapy may provide an approach to complement or replace conventional DC adoptive cell therapy for suppressing tumor growth.

History

Journal

Gene therapy

Volume

6

Pagination

1835-1844

Location

London, Eng.

ISSN

0969-7128

eISSN

1476-5462

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

1999, Stockton Press

Issue

11

Publisher

Stockton Press