2.50
Hdl Handle:
http://hdl.handle.net/10541/78387
Title:
Use of adenoviruses encoding CD40L or IL-2 against B cell lymphoma.
Authors:
Meziane, El-Kahina; Bhattacharyya, Tapan; Armstrong, Anne C; Qian, Cheng; Hawkins, Robert E; Stern, Peter L; Dermime, Said
Abstract:
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.
Affiliation:
CRUK Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.
Citation:
Use of adenoviruses encoding CD40L or IL-2 against B cell lymphoma. 2004, 111 (6):910-20 Int. J. Cancer
Journal:
International Journal of Cancer
Issue Date:
10-Oct-2004
URI:
http://hdl.handle.net/10541/78387
DOI:
10.1002/ijc.20332
PubMed ID:
15300803
Type:
Article
Language:
en
ISSN:
0020-7136
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMeziane, El-Kahina-
dc.contributor.authorBhattacharyya, Tapan-
dc.contributor.authorArmstrong, Anne C-
dc.contributor.authorQian, Cheng-
dc.contributor.authorHawkins, Robert E-
dc.contributor.authorStern, Peter L-
dc.contributor.authorDermime, Said-
dc.date.accessioned2009-08-24T15:20:24Z-
dc.date.available2009-08-24T15:20:24Z-
dc.date.issued2004-10-10-
dc.identifier.citationUse of adenoviruses encoding CD40L or IL-2 against B cell lymphoma. 2004, 111 (6):910-20 Int. J. Canceren
dc.identifier.issn0020-7136-
dc.identifier.pmid15300803-
dc.identifier.doi10.1002/ijc.20332-
dc.identifier.urihttp://hdl.handle.net/10541/78387-
dc.description.abstractSome 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.en
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAdenoviridae-
dc.subject.meshAnimals-
dc.subject.meshAntibody Formation-
dc.subject.meshAntigen Presentation-
dc.subject.meshCD40 Ligand-
dc.subject.meshCancer Vaccines-
dc.subject.meshFemale-
dc.subject.meshFibroblasts-
dc.subject.meshHumans-
dc.subject.meshImmunity, Cellular-
dc.subject.meshImmunotherapy-
dc.subject.meshInterleukin-2-
dc.subject.meshLymphoma, B-Cell-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshPhenotype-
dc.subject.meshSpleen-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshUp-Regulation-
dc.titleUse of adenoviruses encoding CD40L or IL-2 against B cell lymphoma.en
dc.typeArticleen
dc.contributor.departmentCRUK Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.en
dc.identifier.journalInternational Journal of Canceren

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