Antigen mimicry by an anti-idiotypic antibody single chain variable fragment

Tripathi, Pulak; Qin, Haiyang; Deng, Su-Jun; Xu, Chengzhi; Bhattacharya‐Chatterjee, Malaya; Foon, Kenneth A.; Chatterjee, S. K.

doi:10.1016/s0161-5890(98)00072-8

Cited by 19 publications

(11 citation statements)

References 25 publications

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“…Trastuzumab, a humanised mAb specific for HER-2/neu, whose efficiency has been proven both alone and in combination with various chemotherapeutic agents in women with HER-2-positive metastatic breast cancer (Cobleigh et al, 1999;Slamon et al, 2001), was chosen as Ab1. Several authors have pointed out that a distortion of the scFv derived from a monoclonal anti-Id antibody or the differential orientation of the V H or V L domain in a scFv construct are likely to affect its antigen mimicry (Francisco et al, 1995;Tripathi et al, 1998). For this reason, the phage display technology was chosen to isolate human anti-Id scFv fragments from the synthetic ETH-2 library (Pini et al, 1998) since (i) such scFv do not need further engineering and (ii) they could be used for repeated immunisations of cancer patients without invoking a human anti-mouse antibody response.…”

Section: Discussionmentioning

confidence: 99%

“…It is important to remark that (i) this response would probably be much lower in humans since the extracellular domain of HER-2/neu is shed, circulates in the sera of patients and is available to the immune system for tolerance induction (Leitzel et al, 1992), (ii) the human Fc of the fusion protein is immunogenic in mice but not in humans and (iii) the immunogenicity of anti-Id scFv fragments could be increased by incorporating additional immunogenic sequences such as keyhole limpet haemocyanin (KLH) (Tripathi et al, 1998). Our results with regard to immunisation using anti-Id scFv, either in soluble form or displayed on phage, are in agreement with those of Magliani et al (1998) who described the use of anti-Id scFv antibody (soluble or phage-fused) to mimick the antigenic properties of the type III capsular polysaccharide of group B Streptococcus.…”

Section: Discussionmentioning

confidence: 99%

“…Active immunisation with tumour-specific Id vaccines has very early been shown to inhibit tumour growth in animals (Kennedy et al, 1985). Carcinoembryonic antigen (CEA) mimicry by (i) an anti-Id single-chain variable fragment (scFv) constructed from a murine mAb (Tripathi et al, 1998) and (ii) murine dendritic cells pulsed with anti-Id antibody (Saha et al, 2003) were published with convincing results regarding the level of the humoral response raised in mice. Recently, a study from the same group also described the use of a murine monoclonal anti-Id antibody as a surrogate antigen for human HER-2/neu (Baral et al, 2001).…”

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confidence: 99%

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Isolation and characterisation of a human anti-idiotypic scFv used as a surrogate tumour antigen to elicit an anti-HER-2/neu humoral response in mice

Gauthier

Pugnière

et al. 2004

Br J Cancer

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HER-2/neu is a tumour antigen that is overexpressed in human breast tumours. Among the vaccine strategies developed to overcome immune tolerance to self-proteins, vaccination with anti-idiotypic (anti-Id) antibodies has been described as a promising approach for treatment of several malignant diseases. To develop an active immunotherapy for cancer patients positive for HER-2/ neu, we investigated immunisation with human anti-Id single-chain fragments (scFv) mimicking the conformation of HER-2/neu protein to induce a humoral response in mice. We selected by phage display two human anti-Id scFv (Ab2b) directed against trastuzumab F(ab 0 ) 2 fragments (Ab1), a humanised anti-HER-2/neu monoclonal antibody. Using competitive ELISA and Biacore biosensor analysis, we showed that anti-Id scFv 40 and scFv 69 could inhibit HER-2/neu binding to trastuzumab. Following vaccination of BALB/c mice with the soluble or phage-displayed scFv, Ab3 polyclonal antibodies, and among them Ab1 0 antibodies able to bind HER-2/neu, were detected in the sera of the immunised mice. These results demonstrate that the human anti-Id scFv could act as a surrogate antigen for HER-2/neu. The present study strongly suggests that the novel 30 kDa human mini-antibody could be used as an anti-idiotype-based vaccine formulation to induce an effective humoral response in patients bearing HER-2/neu-positive tumours.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Isolation and characterisation of a human anti-idiotypic scFv used as a surrogate tumour antigen to elicit an anti-HER-2/neu humoral response in mice

Gauthier

Pugnière

et al. 2004

Br J Cancer

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“…With an anti -idiotype antibody mimicking the carcinoembryonic antigen, we found that only one format, VHLnVL, had biological activity. 21 In the 1A7 system, both formats of scFv expressed by the plasmids had nearly equal biological activities, assayed in vitro as well as in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that for the best antigen mimicry of scFv derived from 3H1 Ð an antiidiotype antibody mimicking carcinoembryonic antigen Ð the VH chain should be in the amino terminus of the scFv; VH and VL should be linked by a 15 -amino acid Ln. 21 To explore the possibility that different configurations of scFv of 1A7 might have different in vitro or in vivo effects, two expression vectors were constructed. In the first one, the VH chain was placed at the amino terminal in the construct ( VHLnVL ) and in the other, it was placed at the carboxy terminal in the construct (VLLnVH ).…”

Section: Construction Of Plasmid Vectors Encoding Single -Chain Variamentioning

confidence: 99%

Construction and characterization of DNA vaccines encoding the single-chain variable fragment of the anti-idiotype antibody 1A7 mimicking the tumor-associated antigen disialoganglioside GD2

Zeytin

Tripathi

Bhattacharya‐Chatterjee

et al. 2000

Cancer Gene Ther

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Anti -idiotype antibody, 1A7, functionally mimics the tumor -associated antigen disialoganglioside GD2, which is overexpressed on the surface of a number of neuroectodermal tumors such as melanoma, neuroblastoma, soft tissue sarcoma, and small cell carcinoma of the lung. Immunization of mice with 1A7 generated the production of anti -GD2 antibodies. In a phase I clinical trial, immunization of patients with 1A7, mixed with the adjuvant QS21, demonstrated that 1A7 could act as a surrogate antigen for GD2 and induce strong humoral immune responses in advanced stage melanoma patients. DNA vaccines have recently been shown to invoke humoral as well as cellular responses in injected hosts against the transgene product. To evaluate the efficiency of DNA vaccines encoding anti -idiotype antibodies, we constructed expression plasmids encoding the variable heavy ( VH ) and variable light ( VL ) chains of 1A7. The plasmids were made in two configurations, expressing either the VH ( pc1A7VHLnVL ) or the VL ( pc1A7VLLnVH ) chain of 1A7 at the amino terminus, linked together by a 15 -amino acid linker ( Ln ) . In vitro transcription / translation assays and transfection of CHO -K1 cells with the plasmids demonstrated that a $30 -kDa protein was expressed by both configurations of the single -chain variable fragment. This protein can be specifically precipitated by monoclonal anti -GD2 antibody, 14G2a. Following intramuscular injection in mice, the plasmids were detectable in the injected tissues for at least 3 months and the injected plasmids actively transcribed the single -chain variable fragment 1A7 gene at the injected site. A single, intramuscular immunization of a group of C57BL / 6 mice with pc1A7VLLnVH in phosphate -buffered saline induced humoral immune responses against 1A7 as well as GD2, the nominal antigen. Multiple immunizations, however, were required to elicit stronger immune responses.

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