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

Abstract

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.

TargetingO-Acetyl-GD2 Ganglioside for Cancer Immunotherapy

“…Thus, anti-idiotype antibodies can act as antigens, inducing a response against the original antigen. A remarkable advantage of anti-idiotype mAbs is the fact that the constant regions of the anti-idiotypic antibody can serve to boost antitumor immune responses [97]. This is a useful strategy to induce an antibody response towards a ganglioside, which is a weak immunogenic molecule in itself.…”

Recapitulation of the anti-Idiotype antibodies as vaccine candidate

“…Curative access to varied sort of cancers is primarily gained through the idiotypic network hypothesis, involving immunization achieved through antitumor Ab1 antibodies bringing about the production of anti-idiotypic antibodies (Ab2), or given anti-idiotypic antibodies (Ab2), which be working as anti-idiotypic vaccines which could functionally curtail the tumor-associated antigens (TAA) and evoke strong immune response to tumor cell [35]. A limitation of immunotherapy achieved with TAA will be an induction of comparatively low immunogenicity of tumor antigens.…”

Naive Idiotope-Specific B and T Cells Collaborate Efficiently in the Absence of Dendritic Cells

“…First, perturbations in the balance between Id + and anti-Id Abs have been associated with autoimmune diseases, such as diabetes mellitus (5) and Sjögren's syndrome (6). Second, anti-Id Ab can mimic poorly immunogenic Ag and, thus, may be used as surrogate Ag for vaccination purposes (7). Third, induction of anti-Id Abs by idiotype vaccination with tumor Ig constitutes a promising therapeutic strategy in B cell lymphoma patients (8).…”