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Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

Necdet Uskent ()
Nil Molinas Mandel ()
Zafer Gulbas ()
Gulcan Baloglu ()
Barkın Berk ()
Ruchan Uslu ()
Aziz Yazar ()
Huseyin Baloglu ()


Aberrant accumulation of a specific sialic acid has been shown to exist in many human malignant cell membranes termed as N-glycolyl neuraminic acid (NeuGc). This particular ganglioside do not normally exist in normal human cells, due to the lack of an enzyme (cytidine monophospho-N-acetyl-neuraminic acid) which is responsible for the synthesis of N—glycolyl neurominic acid. The aberrant expression of NeuGcGM3 ganglioside in the cell surface of certain human tumors, made this molecule an attractive target for immunotherapy. By using 14 F7 monoclonal antibody directed to identify NeuGcGM3 in the tumor tissue, it is possible to select patients for anti-NeuGcGM3 immunotherapy. Racotumomab is an anti-idiotype vaccine, being a mirror image of NeuGcGm3 mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside.

In this study, we monitored 12 patients with advanced non-small cell lung cancer (NSCLC) who are on racotumomab vaccine maintenance following chemotherapy. Cytotoxic tests with vaccinated patients’ sera were performed using L1210 cell lines at the 3rd, 6th, 9th, and 12thmonths of vaccination and the results were compared with clinical outcomes. Serum antibodies to NeuGcGm3 ganglioside were also checked before initiation and thereafter with the same intervals. The aim of the study was to investigate the value of antibodies and cytotoxic test as biomarkers for treatment outcome. Our observation confirmed that consistently higher cytotoxicity rates in the cell culture correlated with better progression free survivals of the patients who are on racotumomab maintenance.


racotumomab; cytotoxic tests with hyperimmune patients’ sera; non-small cell lung cancer; cancer vaccines

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Irie A, Koyama S, Kozutsumi Y, Kawasaki T, Suzuki A. The molecular basis for the absence of N-glycolylneuraminic acid in humans. J Biol Chem 1998; 273(25): 15866–15871. doi: 10.1074/jbc.273.25.15866.

Vazquez AM, Alfonso M, Lanne B, Karlsson KA, Carr A, et al. Generation of murine monoclonal antibody specific for N-glycolylneuraminic acid containing gangliosides that also recognizes sulfated glycolipids. Hybridoma. 1995; 14(6): 551–556. doi: 10.1089/hyb.1995.14.551.

Blanco R. Aberrant Expression of N-Glycolyl GM3 ganglioside in hepatocellular carcinoma. J Mol Biomark Diagn 2016; 7(6). doi: 10.4172/2155-9929.1000i101.

Blanco R. N-Glycolyl GM3 ganglioside as a relevant tumor antigen in humans. J Mol Biomark Diagn 2016; 7(6):1000e124. doi: 10.4172/2155-9929.1000e124.

Carr A, Mullet A, Mazorra Z, Vazquez AM, Alfonso M, et al. A mouse IgG1 monoclonal antibody specific for N-glycolyl GM3 ganglioside recognized breast and melanoma tumors. Hybridoma. 2004; 19(3): 241–247. doi: 10.1089/02724570050109639.

Blanco R, Rengifo E, Cedeño M, Rengifo CE, Alonso DF, et al. Immunoreactivity of the 14F7 mab raised against N-glycolyl GM3 ganglioside in epithelial malignant tumors from digestive system. ISRN Gastroenterology 2011; 2011(2011): Article ID 645641. doi:10.5402/2011/645641.

Tangvoranuntakul P, Gagneux P, Diaz S, Bardor M, Varki N, et al. Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc Natl Acad Sci USA 2003; 100(21): 12045–12050. doi: 10.1073/pnas.2131556100.

Yin J, Hashimoto A, Izawa M, Miyazaki K, Chen, GY, et al. Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells. Cancer Res 2006; 66(6): 2937–2945. doi: 10.1158/0008-5472.CAN-05-2615.

de León J, Fernández A, Mesa C, Clavel M, Fernández LE. Role of tumour-associated N-glycolylated variant of GM3 ganglioside in cancer progression: Effect over CD4 expression on T cells. Cancer Immunol Immunother 2006; 55(4): 443–450. doi: 10.1007/s00262-005-0041-6.

Blanco R, Domínguez E, Morales O, Blanco D, Martínez D, et al. Prognostic significance of N-Glycolyl GM3 ganglioside expression in non-small cell lung carcinoma patients: new evidences. Pathol Res Int 2015; 2015(2015): Article ID 132326. doi:10.1155/2015/132326.

Blanco R, Cedeno M, Rengifo CE, Blanco D, Frometa M, et al. Double expression of epidermal growth factor receptor and N-Glycolyl GM3 ganglioside in human malignant tumors. Adv Mol Diag 2012; 2(1): 2–6

Hakomori S. Tumor malignancy defined by aberrant glycosylation and sphingo (glycol) lipid metabolism. Cancer Res 1996; 56(23): 5309–5318.

Mannhalter JW, Neychev HO, Zlabinger JG, Ahmad R, Martha M. Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminum hydroxide: Effect on antigen uptake and antigen presentation. Clin Exp Immunol 1985; 61: 143–151.

Diaz A, Alfonso M, Alonso R, Saurez G, Troche M, et al. Immune responses in breast cancer patients immunized with an anti-idiotype antibody mimicking neugc-containing gangliosides. Clin Immunol 2003; 107(2): 80–89. doi: 10.1016/S1521-6616(03)00036-6.

Rodriguez-Zhurbenko N, Martinez D, Blanco R, Rondón T, Griñán T, et al. Human antibodies reactive to NeuGcGM3 ganglioside have cytotoxic anti-tumor properties. Euepean J Immunol 2013; 43(3): 826–837. doi: 10.1002/eji.201242693.

Jerne NK. Towards a network theory of the immune system. Ann Immunol (Paris) 1974; 125C(1–2): 373–389.

Hernandez AM, Rodriguez N, Gonzalez JE, Reyes E, Rondon T, et al. Anti-neugcgm3 antibodies, actively elicited by idiotypic vaccination in non-small cell lung cancer patients, induce tumor cell death by an oncosis-like mechanism. J Immunol 2011; 186(6): 3735–3744. doi: 10.4049/jimmunol.1000609.

Alfonso S, Diaz RM, de la Torre A, Santiesteban E, Aguirre F, et al. Anti-idiotype vaccine in non-small cell lung cancer: Experience in stage IIIb/IV patients. Cancer Biol Ther 2007; 6(12): 1847–1852.doi: 10.4161/cbt.6.12.5000.

Macías A Alfonso S, Santiesteban E, Viada C, Menndoza I, et al. Active specific immunotherapy with racotumomab in the treatment of advanced non-small cell lung cancer (NSCLC). European Society of Medical Oncology; 2012 Sep 29–Oct 2; Vienna, Austria. Abstract 1472.

Osorio M, Gracia E, Reigosa E, Hernandez J, de la Torre A, et al. Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma. Cancer Manag Res 2012; 4: 341–345. doi: 10.2147/CMAR.S22617.

Alfonso S, Valdés-Zayas A, Santiesteban ER, Flores YI, Areces F, et al. A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small-cell-lung cancer patients. Clin Cancer Res 2014; 20(14): 3660–3671. doi: 10.1158/1078-0432.CCR-13-1674.

Vázquez AMH Rodrèguez-Zhurbenko N, López AMV. Anti-ganglioside anti-idiotypic vaccination: more than molecular mimicry. Front Oncol 2012; 2: 170. doi: 10.3389/fonc.2012.00170.



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