Use of adenoviruses encoding CD40L or IL-2 against B cell lymphoma.
Authors
Meziane, El-KahinaBhattacharyya, Tapan
Armstrong, Anne C
Qian, Cheng
Hawkins, Robert E
Stern, Peter L
Dermime, Said
Affiliation
CRUK Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.Issue Date
2004-10-10
Metadata
Show full item recordAbstract
Some B cell lymphomas lack important costimulatory properties that could prevent them from being used as cell based vaccines. Infection of A20 B lymphoma cells with a replication-defective adenovirus encoding murine (m) CD40L, but not mIL-2, produces an antigen presentation phenotype with upregulation of MHC Class I/II, induction of B7-1/2 molecules and production of MIL-12 and MIP-1alpha. Subcutaneous vaccination with irradiated Ad-mCD40L-infected- or Ad-mIL-2-infected-A20 cells generated A20-specific CD8+ T cell responses and cross reactive A20 Ig antibodies. Only vaccination with Ad-mCD40L-infected A20 cells produced a significant delay in tumor growth and long-term survival (p = 0.0039). Stronger protective immunity to A20 challenge was generated by intravenous priming with A20 cells infected with Ad-mCD40L, Ad-mIL-2 or their combination followed by a boost immunization with A20 cells activated with syngeneic fibroblasts expressing CD40L. Compared to Ad-LacZ-infected A20 priming, the combination priming was most effective followed by Ad-mCD40L and Ad-mIL-2 (p = 0.0027, p = 0.0027, p = 0.0163 respectively). Significant A20-specific CD8+ T cell-mediated cytotoxicity was only demonstrated in splenocytes from these groups of vaccinated animals. By contrast, ELISPOT assay of splenocytes from all A20 prime/boosted vaccinated groups demonstrated increases in gamma-interferon release by T cells elicited by in vitro stimulation either with A20 cells or another syngeneic 2PK-3 lymphoma, indicating the presence of cross reactive immunity. Similarly anti-A20 immunoglobulin antibodies generated after vaccination were not necessarily A20 idiotype-specific. Direct therapy of pre-established tumors was achieved with the combination of Ad-mCD40L and Ad-mIL-2 given at Days 4 and 8 at the tumor site with a significant long-term survival of 85% of tumor-bearing mice (p = 0.0001). Our study strongly supports the use of Ad-CD40L and Ad-IL-2 combination therapy for the treatment of patients with B cell lymphoma.Citation
Use of adenoviruses encoding CD40L or IL-2 against B cell lymphoma. 2004, 111 (6):910-20 Int. J. CancerJournal
International Journal of CancerDOI
10.1002/ijc.20332PubMed ID
15300803Type
ArticleLanguage
enISSN
0020-7136ae974a485f413a2113503eed53cd6c53
10.1002/ijc.20332
Scopus Count
Collections
Related articles
- CpG oligodeoxynucleotides enhance the capacity of adenovirus-mediated CD154 gene transfer to generate effective B-cell lymphoma vaccines.
- Authors: Rieger R, Kipps TJ
- Issue date: 2003 Jul 15
- In vivo antitumor effect of CD40L-transduced tumor cells as a vaccine for B-cell lymphoma.
- Authors: Briones J, Timmerman J, Levy R
- Issue date: 2002 Jun 1
- Immunization with a recombinant adenovirus encoding a lymphoma idiotype: induction of tumor-protective immunity and identification of an idiotype-specific T cell epitope.
- Authors: Armstrong AC, Dermime S, Allinson CG, Bhattacharyya T, Mulryan K, Gonzalez KR, Stern PL, Hawkins RE
- Issue date: 2002 Apr 15
- Antitumor immunity after vaccination with B lymphoma cells overexpressing a triad of costimulatory molecules.
- Authors: Briones J, Timmerman JM, Panicalli DL, Levy R
- Issue date: 2003 Apr 2
- Transgenic expression of CD40L and interleukin-2 induces an autologous antitumor immune response in patients with non-Hodgkin's lymphoma.
- Authors: Takahashi S, Yotnda P, Rousseau RF, Mei Z, Smith S, Rill D, Younes A, Brenner MK
- Issue date: 2001 May