Anti-idiotypic DNA vaccines for lymphoma immunotherapy require the presence of both variable region genes for tumor protection

Benvenuti, Federica; Burrone, Óscar R.; Efremov, Dimitar G.

doi:10.1038/sj.gt.3301133

Cited by 30 publications

(32 citation statements)

References 27 publications

(21 reference statements)

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“…The antiId BCL1 antibodies induced by our scFv DNA vaccination were previously shown to induce protection against tumour challenge. 7 In this report, we show that these antibodies are directed exclusively against conformational combined V L /V H determinants. Although it is likely that most anti-Id antibodies recognise epitopes formed by combined V L /V H sequences, it cannot be excluded that some recognise determinants on a single V region, whose conformations are strictly dependent on the other V region partner.…”

Section: Discussionmentioning

confidence: 62%

“…Our laboratory has demonstrated that, in the murine BCL1 lymphoma model, genetic vaccination with a construct containing the Id BCL1 in a scFv format, fused to the CH3 exon of the human IgG1 constant region was able to induce high titres of anti-Id antibodies and resistance to tumour challenge. 7 We showed that both tumourderived V regions were essential for the induction of protective immunity.…”

Section: Introductionmentioning

confidence: 95%

“…7 The gene construct contained the two BCL1 variable regions in the V L -V H orientation, separated by an 18-amino acid linker that ensures optimal folding of the scFv molecules.…”

Section: Induction Of Anti-id Antibodies By Scfv Dna Immunisationmentioning

confidence: 99%

“…7 20 that contains the C-terminal region of the short isoform of human membrane IgE ⑀H chain (⑀CH4, EMPD, transmembrane and cytoplamic domains).…”

Section: Idiotypic Constructsmentioning

confidence: 99%

“…In the case of surface Ig + B cell malignancies, such as B cell lymphomas, idiotypes are therefore ideal tumour-associated antigens that can be used as targets for immunotherapy. Active immunisation using idiotypic protein [1][2][3] and more recently, genetic immunisation with plasmid DNA encoding tumour-derived Ig variable regions [4][5][6][7] was found to be effective in inducing anti-Id antibodies and protection against tumour challenge. Our laboratory has demonstrated that, in the murine BCL1 lymphoma model, genetic vaccination with a construct containing the Id BCL1 in a scFv format, fused to the CH3 exon of the human IgG1 constant region was able to induce high titres of anti-Id antibodies and resistance to tumour challenge.…”

Section: Introductionmentioning

confidence: 99%

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Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined VL/VH determinants

Benvenuti

2001

Gene Ther

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 95%

“…7 The gene construct contained the two BCL1 variable regions in the V L -V H orientation, separated by an 18-amino acid linker that ensures optimal folding of the scFv molecules.…”

Section: Induction Of Anti-id Antibodies By Scfv Dna Immunisationmentioning

confidence: 99%

“…7 20 that contains the C-terminal region of the short isoform of human membrane IgE ⑀H chain (⑀CH4, EMPD, transmembrane and cytoplamic domains).…”

Section: Idiotypic Constructsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined VL/VH determinants

Benvenuti

2001

Gene Ther

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Use of adenoviruses encoding CD40L or IL‐2 against B cell lymphoma

Meziane

Bhattacharyya

Armstrong

et al. 2004

Intl Journal of Cancer

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؉ 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 ␥-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.

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DNA vaccination against tumors

Prud’homme

2004

The Journal of Gene Medicine

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DNA vaccines have been used to generate protective immunity against tumors in a variety of experimental models. The favorite target antigens have been those that are frequently expressed by human tumors, such as carcinoembryonic antigen (CEA), ErbB2/neu, and melanoma-associated antigens. DNA vaccines have the advantage of being simple to construct, produce and deliver. They can activate all arms of the immune system, and allow substantial flexibility in modifying the type of immune response generated through codelivery of cytokine genes. DNA vaccines can be applied by intramuscular, dermal/epidermal, oral, respiratory and other routes, and pose relatively few safety concerns. Compared to other nucleic acid vectors, they are usually devoid of viral or bacterial antigens and can be designed to deliver only the target tumor antigen(s). This is likely to be important when priming a response against weak tumor antigens. DNA vaccines have been more effective in rodents than in larger mammals or humans. However, a large number of methods that might be applied clinically have been shown to ameliorate these vaccines. This includes in vivo electroporation, and/or inclusion of various immunostimulatory molecules, xenoantigens (or their epitopes), antigen-cytokine fusion genes, agents that improve antigen uptake or presentation, and molecules that activate innate immunity mechanisms. In addition, CpG motifs carried by plasmids can overcome the negative effects of regulatory T cells. There have been few studies in humans, but recent clinical trials suggest that plasmid/virus, or plasmid/antigen-adjuvant, prime-boost strategies generate strong immune responses, and confirm the usefulness of plasmid-based vaccination.

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Anti-idiotypic DNA vaccines for lymphoma immunotherapy require the presence of both variable region genes for tumor protection

Cited by 30 publications

References 27 publications

Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined VL/VH determinants

Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined VL/VH determinants

Use of adenoviruses encoding CD40L or IL‐2 against B cell lymphoma

DNA vaccination against tumors

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