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Immunotherapy for murine K1735 melanoma: combinatorial use of recombinant adenovirus expressing CD40L and other immunomodulators.

Abstract：

:We have constructed and tested five recombinant adenoviruses (Ads) that express a variety of immunomodulators, including CD40 ligand (CD40L), a potent costimulator of several components of the immune system. We demonstrate that CD40L expressed from Ad in K1735 mouse melanoma cells leads to a strong reduction in tumorigenicity and to efficient protective immunity in a vaccination setting. Subsequently, using a therapeutic approach, we found that local, intratumoral coinjection of CD40L- and IL-2-expressing Ads was superior to any other agents tested and resulted in an at least 1.9-fold increase in mean survival time, in contrast to systemic application of recombinant CD40L or GM-CSF proteins, which had no significant effects. When using vaccination as a therapeutic approach, the combinations of CD40L plus IL-2 or GM-CSF plus IL-2 from Ad gave rise to an extended (2.8-fold) increase in mean survival time. A detailed analysis of immune cells present within regressing tumors indicated that mainly CD4(+) and CD8(+) T cells, and to a lesser extent dendritic cells, infiltrated the tumor mass, but not NK cells, macrophages, or granulocytes. These results propose that a combination of CD40L plus IL-2 has an improved efficacy over the use of single agents when applied for direct in situ therapy or vaccination therapy.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Peter I,Nawrath M,Kamarashev J,Odermatt B,Mezzacasa A,Hemmi S

doi

10.1038/sj.cgt.7700475

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

597-605

issue

7

eissn

0929-1903

issn

1476-5500

journal_volume

9

pub_type

杂志文章

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