Anti-Idiotype Antibodies in Cancer Treatment

Abstract

Idiotypes, that is the collections of any immunoglobulin’s specific epitopes, have been historically used in different ways for cancer treatment as immunotherapy tools. Inherently, the way they are actually employed mostly depends on the type of tumor cell target. The first such attempts consisted in the administration of monoclonal, anti-idiotype antibodies to patients with B-cell-lymphoma. They were able to show clinical activity, but were later abandoned due to both logistical constrains and the emergence of idiotype variants which could escape their action. Later, idiotype antibodies were also used as vaccines to stimulate the patient’s immune system against the same type of tumors, a setting in which our group has provided the first formal proof of principle of clinical benefit associated with the use of a human cancer vaccine. Several approaches to enhance the efficacy of these idiotype vaccines have been described in recent years, some of them with encouraging results. Meanwhile, new emerging immunotherapeutic strategies have been developed to target idiotypes mimicking idiotype-unrelated, tumor-associated or tumor-specific antigens displayed by several types of solid tumors. The results from those studies seem to support the concept of a decreased self-tolerance against these antigens when vaccination is successful. Of course, it remains of capital importance to better define what successful vaccination means. For instance, it is not clear whether the induction of an idiotype-specific humoral and/or cellular response needs to be documented to imply clinical efficacy or whether the latter may be achieved even when the former cannot be formally demonstrated. All in all, due to the wide application potential of idiotype-based immunotherapy, by means of this review we intend to cover both main achievements and open questions respectively obtained and still been faced by this experimental line of clinical research.