Anti-idiotype antibodies in cancer treatment

Abstract

As a cancer immunotherapy tool, idiotypes (Ids) have been used in different ways over the last three decades, depending on the actual human tumor cell target. It all started with passive, monoclonal, anti-Id antibody treatment of B-cell lymphoma, a setting in which results were tantalizing, but logistics unsustainable. It then moved toward the development of anti-Id vaccines for the treatment of the same tumors, a setting in which we have recently provided the first formal proof of principle of clinical benefit associated with the use of a human cancer vaccine. Meanwhile, it also expanded in the direction of exploiting the antigenic mimicry of some Ids with Idunrelated, tumor-associated antigens for the immunotherapy of a number of solid tumors, a setting in which clinical results are still far from being consolidated. All in all, over the years Id-based immunotherapy has paved the way for a number of seminal therapeutic improvements for cancer patients, including the development of most if not all Id-unrelated monoclonal antibodies that have recently revolutionized the field.

The production of monovalent and anti-idiotype antivenom against Mesobuthus eupeus (Scorpionida: Buthidae) venom in rabbits

“…The use of anti-idiotype antibody in the control of K88 Eschershia coli (Jaradat et al, 2010), Edwardsiella tarda (Qin et al, 2010), hepatitis B (Yildrim et al, 2004, HIV-1 (Mader and Kunert, 2012), prion diseases (Venturini et al, 2009), cancer (Cerio et al, 2007) and atherosclerosis (Brito et al, 2012) were reported before.…”

Immunotherapy of Malignant Disease with Tumor Antigen–Specific Monoclonal Antibodies

“…An alternative, although not exclusive possibility is represented by the induction of anti-idiotypic antibodies, i.e. antibodies specific for the variable region of the administered TA-specific mAb [50,51]. In some cases, these anti-idiotypic antibodies may mimic the TA recognized by the original TA-specific mAb and function as a surrogate antigen [50,51].…”

Vaccination with human anti-trastuzumab anti-idiotype scFv reverses HER2 immunological tolerance and induces tumor immunity in MMTV.f.huHER2(Fo5) mice

“…In clinical trials, including patients with ovarian carcinoma, colorectal carcinoma or malignant melanoma, anti-Id-specific humoral and/or cellular responses following immunization were associated with a better survival rate without toxicity, but with modest objective responses. Available results of treatment of breast cancer patients with anti-Id mAbs are still very preliminary and conclusions go no further than the mere biologic proof of principle [20]. …”