We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Immune properties of recombinant vaccinia virus encoding CD154 (CD40L) are determined by expression of virally encoded CD40L and the presence of CD40L protein in viral particles.
- Authors
Bereta, Michal; Bereta, Joanna; Park, Jonas; Medina, Freddy; Kwak, Heesun; Kaufman, Howard L
- Abstract
Expression of costimulatory molecules by recombinant poxviruses is a promising strategy for enhancing therapeutic vaccines. CD40-CD40L interactions are critical for conditioning dendritic cells (DC) and priming T- and B-cell immunity. We constructed a vaccinia virus expressing murine CD40L (rV-CD40L) and studied its immunomodulatory properties in vitro. Direct DC infection with control vaccinia or psoralen/UV-inactivated rV-CD40L stimulated high levels of interleukin 12 (IL-12) release. However, replication-competent rV-CD40L did not stimulate IL-12 under similar conditions. We observed a high level of CD40L protein on purified viral particles and demonstrated that induction of IL-12 by nonreplicating rV-CD40L was blocked by anti-CD40 antibodies suggesting that functional CD40L on viral particles contributed to alterations in IL-12 synthesis.Since cross-presentation of tumor-associated antigens by DC is augmented by viral infection of tumor cells, we infected MC38 murine colon carcinoma cells with rV-CD40L. Infected cells stimulated IL-12 secretion by DC and proliferation of B cells and DX5+ (NK/NKT) cells through direct CD40-CD40L interaction. A subpopulation of NKT cells expressing CD40 (NK1.1+, CD3lo) appeared to be a major effector population responding to MC38/rV-CD40L. These results highlight the complex immune regulatory effects of rV-CD40L defined by the cumulative effects of CD40L expression, presence of CD40L protein in viral particles, and the replication potential of the virus.Cancer Gene Therapy (2004) 11, 808-818. doi:10.1038/sj.cgt.7700762 Published online 10 September 2004
- Subjects
VACCINIA; VIRUS diseases in cattle; POXVIRUS diseases; RECOMBINANT poxviruses; RECOMBINANT viruses; GENE therapy; CANCER treatment; CANCER genetics
- Publication
Cancer Gene Therapy, 2004, Vol 11, Issue 12, p808
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/sj.cgt.7700762