Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2010, Article ID 814397, 8 pages doi:10.1155/2010/814397
Review Article NGcGM3 Ganglioside: A Privileged Target for Cancer Vaccines Luis E. Fernandez,1 Mariano R. Gabri,2 Marcelo D. Guthmann,3 Roberto E. Gomez,3 Silvia Gold,4 Leonardo Fainboim,5 Daniel E. Gomez,2 and Daniel F. Alonso2 1 Vaccine
Department, Center of Molecular Immunology, Havana 11600, Cuba of Molecular Oncology, Quilmes National University, Roque Saenz Pe˜na 352, Bernal B1876BXD Buenos Aires, Argentina 3 Elea Laboratories, C1417AZE Buenos Aires, Argentina 4 Chemo-Romikin, C1061ABC Buenos Aires, Argentina 5 Division of Immunogenetics, Jos´ e de San Mart´ın Clinics Hospital, University of Buenos Aires, C1120AAF Buenos Aires, Argentina 2 Laboratory
Correspondence should be addressed to Daniel F. Alonso, dfalonso@unq.edu.ar Received 12 July 2010; Accepted 24 September 2010 Academic Editor: Taro Kawai Copyright © 2010 Luis E. Fernandez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc) gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the antiNGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10) and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGcgangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included.
1. Ganglioside-Based Cancer Vaccines The field of cancer vaccines definitively changed after April 2010 when the US Food and Drug Administration (FDA) approved Provenge (sipuleucel-T), a vaccine for advanced prostate cancer patients [1]. For the first time sipuleucelT convincingly increased overall survival by about four months in a randomized Phase III trial conducted in 512 patients. While this immunotherapeutic agent is relatively inconvenient as a personalized vaccine, it seems that selecting the recombinant version of the prostatic acid phosphatase (PAP)—expressed in 95% of prostatic tumor cells—as antigen was critical [2], reaffirming target selection as a key feature in cancer vaccine design. Reasoning in the same way, gangliosides, a broad family of structurally related glycolipids, were firstly suggested as potential targets for cancer immunotherapy [3, 4] based on their higher abundance in tumors when compared with the matched normal tissues. Disappointingly, at the beginning of the present century the failure of the best developed ganglioside-based cancer vaccine for that time, GMK [5], irradiated an unfavorable risky perception to all the projects
in the field, even those not related with the target antigen, the GM2 ganglioside. Nevertheless, in these days ganglioside cancer vaccinologists were facing a kind of “polarization” of positions in view of new facts. Eggermont et al. reported an earlier stop of the Phase III GMK vaccine clinical trial in stage II melanoma patients because the Independent Data Monitoring Committee detected an inferior survival rate for the vaccine arm [6]. While difficult to interpret with respect to potential detrimental effects, this result was considered as a significant setback for ganglioside-based specific immunotherapy in melanoma. In the opposite side, a more optimistic outlook of gangliosides as targets for active immunotherapy of cancer came from the recent work by Cheever et al., who reported in 2009 the National Cancer Institute pilot project for prioritization of cancer antigens [7]. From the selected 75 representative antigens, 4 were gangliosides (GD2, GD3, fucosyl-GM1, and N-acetyl-GM3), ranking between positions 12 and 48. As an overall, at the present moment only two Nglycolyl (NGc) ganglioside-based vaccines, the focus of this paper, are currently tested in Phase III clinical trials [8].