Monoclonal anti-idiotypic antibody mimicking the gastrointestinal carcinoma-associated epitope CO17-1A elicits antigen-specific humoral and cellular immune responses in colorectal cancer patients

Birebent, Brigitte; Mitchell, Edith; Akis, Nese; Li, Weiping; Somasundaram, Rajasekharan; Purev, Enkhtsetseg; Hoey, D. E. Elaine; Mastrangelo, Michael J.; Maguire, Henry; Harris, David T.; Nair, Sridhar; Cai, Dewei; Zhang, Tianqian; Herlyn, Dorothee

doi:10.1016/s0264-410x(02)00752-1

Cited by 14 publications

(7 citation statements)

References 26 publications

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“…The safety and immunogenicity of KLH-coupled anti-idiotypic antibodies in cancer patients has been well established [4, 32], whereas there is no clinical experience with MAP. The results obtained with MAP in mice and humans predict that they should display a similar immunogenicity and safety in patients with malignant diseases.…”

Section: Discussionmentioning

confidence: 99%

Peptides mimicking GD2 ganglioside elicit cellular, humoral and tumor-protective immune responses in mice

Wondimu

Zhang

Kieber‐Emmons

et al. 2007

Cancer Immunol Immunother

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Introduction Because of its restricted distribution in normal tissues and its high expression on tumors of neuroectodermal origin, GD2 ganglioside is an excellent target for active specific immunotherapy. However, GD2 usually elicits low-titered IgM and no IgG or cellular immune responses, limiting its usefulness as a vaccine for cancer patients. We have previously shown that anti-idiotypic monoclonal antibody mimics of GD2 can induce antigen-specific humoral and cellular immunity in mice, but inhibition of tumor growth by the mimics could not be detected. Methods and results Here, we isolated two peptides from phage display peptide libraries by panning with GD2-specific mAb ME361. The peptides inhibited binding of the mAb to GD2. When coupled to keyhole limpet hemocyanin (KLH) or presented as multiantigenic peptides in QS21 adjuvant, the peptides induced in mice antibodies binding specifically to GD2 and delayed-type hypersensitive lymphocytes reactive specifically with GD2-positive D142.34 mouse melanoma cells. Induction of delayed-type hypersensitivity (DTH) reaction was dependent on CD4-positive lymphocytes. The immunity elicited by the peptides significantly inhibited growth of GD2-positive melanoma cells in mice. Conclusion Our study suggests that immunization with peptides mimicking GD2 ganglioside inhibits tumor growth through antibody and/or CD4-positive T cell-mediated mechanisms. Cytolytic T lymphocytes most likely do not play a role. Our results provide the basis for structural analysis of carbohydrate mimicry by peptides.

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Section: Discussionmentioning

confidence: 99%

Peptides mimicking GD2 ganglioside elicit cellular, humoral and tumor-protective immune responses in mice

Wondimu

Zhang

Kieber‐Emmons

et al. 2007

Cancer Immunol Immunother

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“…Specifically, clinical studies with anti-idiotype antibodies mimicking CEA have shown Ab3 immune responses (11,(33)(34)(35) but the benefit for the patients thus far has been limited. Similarly, we have observed only marginal CEA-specific responses following vaccination with the full murine anti-idiotypic mAb 6G6.C4 in patients with R0-resected CEA-positive pancreatic cancers.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal Anti-idiotype Antibody 6G6.C4 Fused to GM-CSF Is Capable of Breaking Tolerance to Carcinoembryonic Antigen (CEA) in CEA–Transgenic Mice

et al. 2005

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“…This study demonstrated that there was a trend for the KLH group to induce higher immune response rates (18/21 and 5/15 patients with anti-anti-Id Abs and T cells, respectively) as compared to the group of patients immunized with the intact IgG (15/23 and 3/15 patients positive). However, clinical responses were rare as this study was undergone on stage IV CRC patients with liver metastasis (Birebent et al, 2001, 2003). …”

Section: Anti-idiotypic Vaccines As Surrogates For Specific Oncogene mentioning

confidence: 99%

Anti-idiotypic antibodies as cancer vaccines: achievements and future improvements

Ladjemi¹

2012

Front. Oncol.

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Since the discovery of tumor-associated antigens (TAAs), researchers have tried to develop immune-based anti-cancer therapies. Thanks to their specificity, monoclonal antibodies (mAbs) offer the major advantage to induce fewer side effects than those caused by non-specific conventional treatments (e.g., chemotherapy, radiotherapy). Passive immunotherapy by means of mAbs or cytokines has proved efficacy in oncology and validated the use of immune-based agents as part of anti-cancer treatment options. The next step was to try to induce an active immune protection aiming to boost own’s host immune defense against TAAs. Cancer vaccines are thus developed to specifically induce active immune protection targeting only tumor cells while preserving normal tissues from a non-specific toxicity. But, as most of TAAs are self antigens, an immune tolerance against them exists representing a barrier to effective vaccination against these oncoproteins. One promising approach to break this immune tolerance consists in the use of anti-idiotypic (anti-Id) mAbs, so called Ab2, as antigen surrogates. This vaccination strategy allows also immunization against non-proteic antigens (such as carbohydrates). In some clinical studies, anti-Id cancer vaccines indeed induced efficient humoral and/or cellular immune responses associated with clinical benefit. This review article will focus on recent achievements of anti-Id mAbs use as cancer vaccines in solid tumors.

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Monoclonal anti-idiotypic antibody mimicking the gastrointestinal carcinoma-associated epitope CO17-1A elicits antigen-specific humoral and cellular immune responses in colorectal cancer patients

Cited by 14 publications

References 26 publications

Peptides mimicking GD2 ganglioside elicit cellular, humoral and tumor-protective immune responses in mice

Peptides mimicking GD2 ganglioside elicit cellular, humoral and tumor-protective immune responses in mice

Monoclonal Anti-idiotype Antibody 6G6.C4 Fused to GM-CSF Is Capable of Breaking Tolerance to Carcinoembryonic Antigen (CEA) in CEA–Transgenic Mice

Anti-idiotypic antibodies as cancer vaccines: achievements and future improvements

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