J Pharm Pharmacogn Res 2(Suppl. 1): S2, 2014
Special supplement with the abstract book of LATINFARMA 2013
CO 002: HUMAN ANTIBODIES REACTIVE TO NEUGCGM3 GANGLIOSIDE HAVE CYTOTOXIC ANTITUMOR PROPERTIES
Rodríguez-Zhurbenko N, Martínez D, Blanco R, Rondón T, Griñán T, Hernández AM.Center of Molecular Immunology, Havana, Cuba. E-mail: firstname.lastname@example.org
Introduction: NeuGcGM3 ganglioside is not naturally expressed in normal human tissues but is overexpressed in several tumors and has immunosuppressive capacity, contributing to cancer progression. These features make NeuGcGM3 an attractive candidate for tumor immunotherapy; however, little is known about the naturally occurring anti-NeuGcGM3 antibody response in healthy humans.
Aims of this study were to analyze and characterize the antibody responses against this ganglioside in healthy donors and cancer patients.
Material and methods: The study comprised 100 healthy donors and 55 age-matched untreated non small cell lung cancer (NSCLC) patients. In all the subjects, specific anti-NeuGcGM3 antibody response was assessed by ELISA. The functionality of these antibodies was tested as their ability to bind and kill tumor cell lines expressing NeuGcGM3.
Results: 65 healthy donors had antibodies that specifically recognized NeuGcGM3 and kill tumor cells expressing this antigen by a complement mediated mechanism. Interestingly, even after complement inactivation, 17% of the positive sera showed a direct cytotoxic effect on the tumor cells. This cytotoxicity was dependent on the presence of the antigen on the tumor cells and resembles an oncotic kind of cell death. Both, the levels of anti-NeuGcGM3 antibodies in the sera of healthy donors as well as the percentage of donors with this natural immunity decrease with age. Furthermore, we could only detect low reactivity against NeuGcGM3 in the sera of 6 NSCLC patients.
Conclusions: Healthy human sera contain naturally occurring antiNeuGcGM3 antibodies with cytotoxic anti-tumor properties, reinforcing the importance of NeuGcGM3 ganglioside as an important target for cancer immunotherapy. Treatments that boosted this antiNeuGcGM3 antibody response should be considered an important immunotherapeutic regimen against NeuGcGM3 containing tumors as elderly donors and NSCLC patients lacked this natural anti-tumor response.