Anti-Idiotype Antibodies in Cancer Treatment


  • M.M. Soldevilla Lab of immunotherapy, Oncology Division, Center for Applied Medical Research
  • A. Lopez-Diaz de Cerio Lab of immunotherapy, Oncology Division, Center for Applied Medical Research
  • S. Inoges Cell Therapy Area, University of Navarra Hospital, University of Navarra, Pamplona, Spain
  • F. Pastor Lab of immunotherapy, Oncology Division, Center for Applied Medical Research
  • H. Villanueva Lab of immunotherapy, Oncology Division, Center for Applied Medical Research
  • M. Bendandi Cell Therapy Area, University of Navarra Hospital, University of Navarra, Pamplona, Spain



Antibody, idiotype, immunotherapy, cancer, lymphoma, solid tumor, vaccine.


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.


Bendandi M. Role of anti-idiotype vaccines in the modern treatment of human follicular lymphoma. Expert Rev Anticancer Ther 2001; 1(1): 65-72.

Bendandi M. The role of idiotype vaccines in the treatment of human B-cell malignancies. Expert Rev Vaccines 2004; 3(2): 163-170.

de Cerio AL, Zabalegui N, Rodriguez-Calvillo M, Inoges S, Bendandi M. Anti-idiotype antibodies in cancer treatment. Oncogene 2007; 26(25): 3594-602.

Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med 1982; 306(9): 517-22.

Meeker T, Lowder J, Cleary ML, et al. Emergence of idiotype variants during treatment of B-cell lymphoma with anti-idiotype antibodies. N Engl J Med 1985; 312(26): 1658-65.

Allebes WA, Knops R, Bontrop RE, et al. Phenotypic and functional changes of tumour cells from patients treated with monoclonal anti-idiotypic antibodies. Scand J Immunol 1990; 32(5): 441-49.

Davis TA, Maloney DG, Czerwinski DK, Liles TM, Levy R. Anti-idiotype antibodies can induce long-term complete remissions in non-Hodgkin's lymphoma without eradicating the malignant clone. Blood 1998; 92(4): 1184-90.

Allebes W, Knops R, Herold M, Huber C, Haanen C, Capel P. Immunotherapy with monoclonal anti-idiotypic antibodies: tumour reduction and lymphokine production. Leuk Res 1991; 15(4): 215-22.

Maloney DG, Brown S, Czerwinski DK, et al. Monoclonal anti-idiotype antibody therapy of B-cell lymphoma: the addition of a short course of chemotherapy does not interfere with the antitumor effect nor prevent the emergence of idiotype-negative variant cells. Blood 1992; 80(6): 1502-10.

Bendandi M. Idiotype vaccines for lymphoma: proof-of-principles and clinical trial failures. Nat Rev Cancer 2009; 9(9): 675-81.

Bendandi M. Aiming at a curative strategy for follicular lymphoma. CA Cancer J Clin 2008; 58(5): 305-17.

Kwak LW, Campbell MJ, Czerwinski DK, Hart S, Miller RA, Levy R. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N Engl J Med 1992; 327(17): 1209-15.

Hsu FJ, Caspar CB, Czerwinski D, et al. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma--long-term results of a clinical trial. Blood 1997; 89(9): 3129-35.

Weng WK, Czerwinski D, Timmerman J, Hsu FJ, Levy R. Clinical outcome of lymphoma patients after idiotype vaccination is correlated with humoral immune response and immunoglobulin G Fc receptor genotype. J Clin Oncol 2004; 22(23): 4717-24.

Weng WK, Czerwinski D, Levy R. Humoral immune response and immunoglobulin G Fc receptor genotype are associated with better clinical outcome following idiotype vaccination in follicular lymphoma patients regardless of their response to induction chemotherapy. Blood 2007; 109(3): 951-53.

Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2(1): 52-58.

Timmerman JM. Vaccine therapies for non-Hodgkin's lymphoma. Curr Treat Options Oncol 2002; 3(4): 307-15.

Kwak LW, Young HA, Pennington RW, Weeks SD. Vaccination with syngeneic, lymphoma-derived immunoglobulin idiotype combined with granulocyte/ macrophage colony-stimulating factor primes mice for a protective T-cell response. Proc Natl Acad Sci USA 1996; 93(20): 10972-77.

Bendandi M, Gocke CD, Kobrin CB, et al. Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med 1999; 5(10): 1171-77.

Barrios Y, Cabrera R, Yanez R, et al. Anti-idiotypic vaccination in the treatment of low-grade B-cell lymphoma. Haematologica 2002; 87(4): 400-407.

Inoges S, Rodriguez-Calvillo M, Zabalegui N, et al. Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma. J Natl Cancer Inst 2006; 98(18): 1292-301.

Inoges S, Lopez-Diaz de Cerio A, Zabalegui N, et al. Prolonged idiotypic vaccination against follicular lymphoma. Leuk Lymphoma 2009; 50(1): 47-53.

Bendandi M. Clinical benefit of idiotype vaccines: too many trials for a clever demonstration? Rev Recent Clin Trials 2006; 1(1): 67-74.

Inoges S, de Cerio AL, Villanueva H, Soria E, Pastor F, Bendandi M. Idiotype vaccines for lymphoma therapy. Expert Rev Vaccines 2011; 10(6): 801-809.

Inoges S, de Cerio AL, Soria E, Villanueva H, Pastor F, Bendandi M. Idiotype vaccines for human B-cell malignancies. Curr Pharm Des 2010; 16(3): 300-307.

Villanueva H, de Cerio AL, Inoges S, Pastor F, Soldevilla MM, Bendandi M. BiovaxID(R): a customized idiotype vaccine for the treatment of B-cell lymphoma. Expert Rev Vaccines 2011; 10(12): 1661-69.

Schuster SJ, Neelapu SS, Gause BL, et al. Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. J Clin Oncol 2011; 29(20): 2787-94.

Inoges S, Rodriguez-Calvillo M, Lopez-Diaz de Cerio A, et al. Feasibility of idiotype vaccination in relapsed B-cell malignancies. Haematologica 2003; 88(12): 1438-40.

Timmerman JM, Czerwinski DK, Davis TA, et al. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood 2002; 99(5): 1517-26.

Timmerman JM, Vose JM, Czerwinski DK, et al. Tumor-specific recombinant idiotype immunisation after chemotherapy as initial treatment for follicular non-Hodgkin lymphoma. Leuk Lymphoma 2009; 50(1): 37-46.

Freedman A, Neelapu SS, Nichols C, et al. Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. J Clin Oncol 2009; 27(18): 3036-43.

Hurvitz SA, Timmerman JM. Recombinant, tumour-derived idiotype vaccination for indolent B cell non-Hodgkin's lymphomas: a focus on FavId. Expert Opin Biol Ther 2005; 5(6): 841-52.

Bertinetti C, Simon F, Zirlik K, et al. Cloning of idiotype immunoglobulin genes in B cell lymphomas by anchored PCR and production of individual recombinant idiotype vaccines in Escherichia coli. Eur J Haematol 2006; 77(5): 395-402.

Bertinetti C, Zirlik K, Heining-Mikesch K, et al. Phase I trial of a novel intradermal idiotype vaccine in patients with advanced B-cell lymphoma: specific immune responses despite profound immunosuppression. Cancer Res 2006; 66(8): 4496-502.

Navarrete MA, Heining-Mikesch K, Schuler F, et al. Upfront immunization with autologous recombinant idiotype Fab fragment without prior cytoreduction in indolent B-cell lymphoma. Blood 2011; 117(5): 1483-91.

Bendandi M, Marillonnet S, Kandzia R, et al. Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma. Ann Oncol 2010; 21(12): 2420-27.

Stevenson FK, Zhu D, King CA, Ashworth LJ, Kumar S, Hawkins RE. Idiotypic DNA vaccines against B-cell lymphoma. Immunol Rev 1995; 145: 211-28.

Stevenson FK, Zhu D, King CA, et al. A genetic approach to idiotypic vaccination for B cell lymphoma. Ann NY Acad Sci 1995; 772: 212-26.

Bendandi M, Rodriguez-Calvillo M, Inoges S, et al. Combined vaccination with idiotype-pulsed allogeneic dendritic cells and soluble protein idiotype for multiple myeloma patients relapsing after reduced-intensity conditioning allogeneic stem cell transplantation. Leuk Lymphoma 2006; 47(1): 29-37.

Inoges S, Lopez-Diaz de Cerio A, Sampol A, et al. Stem cell transplant and idiotypic vaccination for B-cell malignancies. Curr Top Med Chem 2011; 11(13): 1653-60.

Abdalla AO, Kokhaei P, Hansson L, Mellstedt H, Osterborg A. Idiotype vaccination in patients with myeloma reduced circulating myeloma cells (CMC). Ann Oncol 2008; 19(6): 1172-79.

Yi Q, Szmania S, Freeman J, et al. Optimizing dendritic cell-based immunotherapy in multiple myeloma: intranodal injections of idiotype-pulsed CD40 ligand-matured vaccines led to induction of type-1 and cytotoxic T-cell immune responses in patients. Br J Haematol 2010; 150(5): 554-64.

Mohanty K, Saha A, Pal S, et al. Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu. Breast Cancer Res Treat 2007; 104(1): 1-11.

Soriano JL, Batista N, Santiesteban E, et al. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer. Int J Breast Cancer 2011; 2011: 710292.




How to Cite

M.M. Soldevilla, A. Lopez-Diaz de Cerio, S. Inoges, F. Pastor, H. Villanueva, & M. Bendandi. (2012). Anti-Idiotype Antibodies in Cancer Treatment . Journal of Cancer Research Updates, 1(2), 153–161.