Monoclonal anti-idiotypic antibodies that mimic the epitope on gp120 defined by anti-HIV-1 monoclonal antibody 0.5β

Sperlagh, Melinda; Stefano, Kelly; González‐Scarano, Francisco; Liang, Shaohong; Hoxie, James A.; Maruyama, Haruhiko; Prewett, Marie; Matsushita, Shuzo; Herlyn, Dorothee

doi:10.1097/00002030-199312000-00002

Cited by 7 publications

(5 citation statements)

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“…Ab1¢ titers obtained were similar to those reported by previous investigators [24]. These results (3/7 Ab2 mAbs being identified as true Ab2b) are consistent with the previous report by Cheung et al [7] that 3/6 Ab2 mAbs induced anti-GD2 Ab1¢ activity, and they are superior to the 1/5-1/7 experience in other primary antigen systems (CEA [15] and HIV gp 120 [33]). The Ab2b mAbs identified by induction of Ab1¢ in murine recipients were administered to rabbits, and similar results were obtained in terms of induction of specific, high-titer Ab3 (Fig.…”

Section: Discussionsupporting

confidence: 92%

Generation of anti-idiotypic reagents in the EGFRvIII tumor-associated antigen system

Wikstrand

Cole

Crotty

et al. 2002

Cancer Immunol Immunother

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The use of anti-idiotype (anti-id) vaccines for immunotherapy of human cancers is attractive, as immunization with true anti-id reagents (Ab2 beta) has been shown to induce both cellular and humoral immunity, frequently when the original antigen does not, or when a state of anergy to the self-expressed tumor-associated antigen exists. The aim of this study was to investigate the potential of an anti-id vaccine approach to the glioma-associated antigen epidermal growth factor receptor variant III (EGFRvIII) for human clinical trials. By using conventional methodology, seven rat mAbs specific for the binding site of the murine anti-EGFRvIII-specific mAb Y10, as defined by the ability to inhibit the binding of mAb Y10 to EGFRvIII expressed on cells or as purified protein, were generated, and a subset (3/7) was found to be true Ab2 beta, as defined by the ability to induce the formation of antibody directed against EGFRvIII in two species (mouse and rabbit) when used as immunogen. The ability of these three Ab2 beta to elicit a protective anti-tumor response when used as a vaccine in the syngeneic, subcutaneous C57Bl/6-B16mseEGFRvIII tumor model was investigated. Following vaccination with one Ab2 beta mAb (2C7), 6/20 mice failed to develop tumor upon challenge, and 3/20 mice with outgrowing tumors exhibited dramatic regression of incipient tumors. Vaccination with a second mAb (5G8) resulted in one tumor-free survivor and one tumor regressor; vaccination with the third Ab2 beta mAb (7D3) did not confer protection, but did significantly increase the latency period until tumor outgrowth in all vaccinated recipients. The ability of Ab2 beta mAb 2C7 to induce an anti-EGFRvIII response in non-human primates was investigated by using the saponin adjuvant approved for human clinical trial, QS-21. Three of three macaques produced anti-EGFRvIII titers, as detected on EGFRvIII-expressing cells by both ELISA and fluorescence-activated cytometric analysis, following six immunizations with Ab2 beta mAb 2C7 and QS-21. The results obtained confirm that an anti-id response in the EGFRvIII antigen system can be induced in rodents, rabbits, and non-human primates, and it may prove a useful adjunct to immunotherapeutic approaches to EGFRvIII-positive gliomas, breast carcinomas, and non-small-cell lung tumors.

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Section: Discussionsupporting

confidence: 92%

Generation of anti-idiotypic reagents in the EGFRvIII tumor-associated antigen system

Wikstrand

Cole

Crotty

et al. 2002

Cancer Immunol Immunother

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“…In the latter preparation, only a fraction of the Ab2 molecules mimics antigen and the binding avidities of these molecules may be heterogeneous, giving rise to Ab3 with various avidities. Indeed, the Ab3 elicited by monoclonal Ab2 to Abl 0.5ß (25) bound with higher avidity to the antigen as compared to the Ab3 elicited by the polyclonal Ab2; this is reflected by the ability of the Ab3 elicited by the monoclonal Ab2 (25), but not those elicited by the polyclonal Ab2 (this study), to inhibit binding of Abl 0.5ß to either antigen or peptide.…”

Section: Discussionmentioning

confidence: 70%

“…Furthermore, Ab3 isolated on peptide immunoaffinity column also did not show binding or neutralizing activity. In contrast, monoclonal Ab2 to Abl 0.5ß induced virus-neutralizing Ab3 in rabbits (25).…”

Section: Discussionmentioning

confidence: 88%

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Polyclonal Antiidiotypic Antibodies Mimicking gp120 of HIV-1

Sperlagh¹,

Hoxie²,

Maruyama³

et al. 1994

Viral Immunology

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Rabbit antiidiotypic antibodies (Ab2) were produced against anti-HIV-1 antibody 0.5 beta (Ab1), which binds to gp120 of HIV-1 and shows virus-neutralizing activity. The Ab2 bound specifically to the Ab1 and their binding to Ab2 was inhibited by a recombinant fragment of gp120 (PB1) or a peptide (residues 301-324 of gp120), both expressing the Ab1-defined epitope. The Ab2 induced in rats antiantiidiotypic antibodies (Ab3) that were Ab1-like in their binding reactivities to PB1, native gp120 or peptide and shared idiotopes with the Ab1. However, the Ab2 did not induce virus-neutralizing Ab3, probably a reflection of the low avidity of the Ab3 as compared to the Ab1.

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“…Since genetic restrictions on host immune responses to Ab2γ may exist, these selecting methods may limit the therapeutic usefulness of Ab2. Although subsequent induction of Ab3 has been demonstrated to correlate favorably with the clinical outcome of Ab2-exposed cancer patients, [7][8][9] tumor cell destruction is more likely to be mediated mainly by T cells than by antibodies. 10) Thus, the correlation between Ab2 and T cells can be used as a parameter to evaluate the anti-tumor effects of Ab2.…”

mentioning

confidence: 99%

Functional Mimicry of an Anti‐idiotypic Antibody to Nominal Antigen on Cellular Response

Ma¹,

Zhou²,

Wang³

2002

Japanese Journal of Cancer Research

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One concept for immune therapy of cancer involves induction of antigen mimic antibodies to trigger the immune system into a response against the tumor cells. Anti-idiotypic antibodies (Ab2) directed against the antigen-combining site of other antibodies (Ab1) may functionally and even structurally mimic antigen and induce anti-anti-idiotypic immune response. We report here the generation of murine monoclonal antibody (mAb) WJ02 (Ab2) raised against the murine monoclonal immunoglobulin MJ01 (Ab1), which defines ovarian cancer antigen CA125. In enzyme immunoassays the binding of Ab2 to the variable region of Ab1 could be inhibited by CA125. In addition, the mimicry of mAb WJ02 to CA125 on cellular immune response was detected by human peripheral blood cells. The T cells primed by mAb WJ02 or CA125 proliferated in the presence of CA125 or mAb WJ02, respectively. Furthermore, T cells specific to mAb WJ02 could lyse ovarian cancer cells OVCAR-3 that express CA125. Finally, we proved that a patient immunized with mAb MJ01 could induce T cells that recognize mAb WJ02. In summary, we conclude that mAb WJ02 mimics CA125 on cellular response and such functional mimicry is one of the most important criteria to select Ab2 for cancer therapy.

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Monoclonal anti-idiotypic antibodies that mimic the epitope on gp120 defined by anti-HIV-1 monoclonal antibody 0.5β

Cited by 7 publications

References 0 publications

Generation of anti-idiotypic reagents in the EGFRvIII tumor-associated antigen system

Generation of anti-idiotypic reagents in the EGFRvIII tumor-associated antigen system

Polyclonal Antiidiotypic Antibodies Mimicking gp120 of HIV-1

Functional Mimicry of an Anti‐idiotypic Antibody to Nominal Antigen on Cellular Response

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