Cancer vaccines: An update with special focus on ganglioside antigens (Review)

Bitton, Roberto J.; Guthmann, Marcel D; Gabri, Mariano Rolando; Carnero, Ariel J. L.; Alonso, Daniel F.; Fainboim, Leonardo; Gómez, Daniel E.

doi:10.3892/or.9.2.267

Cited by 55 publications

(69 citation statements)

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“…It exists in gangliosides or glycoproteins with the lipid tails or peptide chains inserting into cell membranes, and the trisaccharide is displayed on the cell surface, where it can be recognized by antibodies. GM3 is abundantly expressed on a number of tumors (27), especially malignant melanoma. Therefore, GM3 represents a potential target for immunotherapy of cancers, but immune tolerance to native GM3 is a problem.…”

Section: Resultsmentioning

confidence: 99%

Efficient Metabolic Engineering of GM3 on Tumor Cells by N-Phenylacetyl-d-mannosamine

et al. 2006

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Abnormal carbohydrates expressed on tumor cells, which are referred to as tumor-associated carbohydrate antigens (TACAs), are potential targets for development of cancer vaccines. However, immune tolerance to TACAs has severely hindered progress in this area. To overcome this problem, we have developed a novel immunotherapeutic strategy based on synthetic cancer vaccines and metabolic engineering of TACAs on tumor cells. One critical step of this new strategy is metabolic engineering of cancer, namely to induce expression of an artificial form of a TACA by supplying tumors with an artificial monosaccharide precursor. To identify the proper precursor for this application, N-propionyl, N-butanoyl, N-iso-butanoyl and N-phenylacetyl derivatives of Dmannosamine were synthesized, and their efficiency as biosynthetic precursors to modify sialic acid and induce expression of modified forms of GM3 antigen on tumor cells was investigated. For this purpose, tumor cells were incubated with different N-acyl-D-mannosamines, and modified forms of GM3 expressed on tumor cells were analyzed by flow cytometry using antigen-specific antisera. Nphenylacetyl-D-mannosamine was efficiently incorporated in a time and dose dependent manner to bioengineer GM3 expression by several tumor cell lines including K562, SKMEL-28 and B16-F0. Moreover, these tumor cell lines also showed ManPAc-dependent sensitivity to cytotoxicity medicated by anti-PAcGM3 immune serum and complement. These results provide an important validation for this novel therapeutic strategy. Because N-phenylacetyl GM3-protein conjugates are particularly immunogenic, the combination of an N-phenylacetyl GM3 conjugate vaccine with systemic N-phenylacetyl-D-mannosamine treatment is a promising immunotherapy for future development and application to melanoma and other GM3-bearing tumors. KeywordsMetabolic engineering; cancer vaccine; GM3; D-mannosamine; sialic acid Sialic acids are unique nine-carbon acidic monosaccharides ubiquitously distributed in high animals and human beings (1). The most common form of sialic acids is N-acetyl-D-neuraminic acid (Neu5Ac, also knows as N-acetyl sialic acid). Neu5Ac is a fascinating sugar in that it usually appears at the nonreducing end of cell surface glycans and thus plays forefront roles in various biological functions such as cell proliferation, immune recognition and pathogenic invasion (2-8).

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Section: Resultsmentioning

confidence: 99%

Efficient Metabolic Engineering of GM3 on Tumor Cells by N-Phenylacetyl-d-mannosamine

et al. 2006

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“…Nivo ovog markera u serumu korelira sa progresijom i regresijom bolesti kao odgovor na terapiju, naročito u slabije-diferenciranim i cisadenokarcinomima ovarijuma. Osetljivost u otkrivanju maligne bolesti povećava se ako se pored CA 125 određuje i CEA [27], mada i CA 72-4 može da posluži kao sekundarni marker.…”

Section: Klasifikacija Tumorskih Markera Na Biohemijskoj Osnoviunclassified

“…Zbog toga, merenje SCCA u serumu svaka tri meseca može biti korisno za izbor terapije. Povećane koncentracije SCCA mogu da se nađu i u karcinomima skvamoznih ćelija pluća [47], ezofagusa i anusa [27].…”

Section: Klasifikacija Tumorskih Markera Na Biohemijskoj Osnoviunclassified

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Ristić¹,

Puhalo-Sladoje²,

Tošović³

2013

Biomedicinska istraž.

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Kratak sadržajUvod. Poslednjih 50 godina, kao rezultat stalnog napretka u istraživanju malignih bolesti, otkrivene su mnoge strukture na tumorskim ćelijama koje se ponašaju kao antigeni. To su makromolekule čija pojava i promene koncentracije ukazuju na genezu i rast malignih tumora i nazivaju se tumorskim markerima. Oni mogu biti strogo specifični, karakteristični samo za jedan tip tumora ili se mogu naći na malignim ćelijama različitih tumora. Često su prisutni i na normalnim ćelijama, bilo samo u pojedinim fazama razvoja ćelije (u embrionalnoj fazi), bilo u smanjenim količinama, ili prikriveni, tako da tek po otkrivanju postaju dostupni ćelijama imunog sistema. Ovi antigeni se nazivaju zajedničkim imenom tumor asocirani antigeni i nisu specifični samo za jedan tumor, već mogu da se javljaju na velikom broju maligno transformisanih ćelija, ali i na nekim normalnim ćelijama. Do sada je opisan veći broj tumor asociranih antigena koji su našli kliničku primenu. Mada još uvek nisu otkriveni tumorski markeri koji su visoko dijagnostički osetljivi i specifični i koji bi mogli da se koriste za otkrivanje karcinoma asimtomatske populacije, njihova pouzdanost u praćenju onkološih bolesnika opravdava kliničku primenu. Ključne riječi: tumorski markeri, klinička primena UvodUprkos velikom napretku u dijagnostici i terapiji, maligni tumori i dalje imaju lošu prognozu i predstavljaju veliki socijalno-medicinski problem. Oko 25% mortaliteta u Evropi i Severnoj Americi čine maligni tumori [1]. Kako je za lečenje malignih bolesti od presudnog značaja njihovo što ranije otkrivanje, ulažu se veliki napori naučne zajednice kako bi se razvile dijagnostičke metode koje bi omogućile ranu dijagnozu malignih tumora. Takozvani "tumorski markeri" su rezultat takvih napora. To su makromolekule čija pojava i promene koncentracije, na neki način, ukazuju na genezu i rast malignih tumora. Mogu biti karakteristični samo za jedan tip tumora ili se mogu naći na malignim ćelijama različitih tumora. Često su prisutni i na normalnim ćelijama, bilo samo u pojedinim fazama razvoja ćelije (u embrionalnoj fazi), bilo u smanjenim količinama, ili prikriveni, tako da

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“…1 Therefore, the search for effective therapeutic cancer vaccines or cancer immunotherapies has been an active area in recent years. [2][3][4][5] Since the early 1970's, many abnormal or excessively expressed glycans have been characterized on cancer cells. 6-9 These glycans, termed tumor-associated carbohydrate antigens (TACAs), play an important role not only in carcinogenic processes, such as cancer cell signaling and adhesion and cancer metastasis, 10-12 but also in the design of new cancer vaccines or cancer immunotherapies.…”

Section: Introductionmentioning

confidence: 99%

“…13-16 Some TACA-based cancer vaccines have been on clinical trials and shown promising clinical results. 4,5,[17][18][19] However, among many TACAs identified, only a few can form functional vaccines via conjugation to a carrier protein. The majority of TACAs are essentially non-immunogenic due to the problem of immune tolerance, but since some tolerated TACAs are relatively abundant on cancer cells, they are useful immunological targets.…”

Section: Introductionmentioning

confidence: 99%

Efficient glycoengineering of GM3 on melanoma cell and monoclonal antibody-mediated selective killing of the glycoengineered cancer cell

Wang

Zhang

Guo

2007

Bioorganic & Medicinal Chemistry

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To verify the principal of a new immunotherapeutic strategy for cancer, a monoclonal antibody 2H3 against N-phenylacetyl GM3, an unnatural form of the tumor-associated antigen GM3, was prepared and employed to demonstrate that murine melanoma cell B16F0 could be effectively glycoengineered by N-phenylacetyl-D-mannosamine to express N-phenylacetyl GM3 and that 2H3 was highly cytotoxic to the glycoengineered B16F0 cell in the presence of complements. It was further demonstrated that B16F0 cell could be glycoengineered 4-5 times more effectively than 3T3 A31 cell, a normal murine embryo fibroblast cell, and that the antibody and complement mediated cytotoxicity was at least 200 times more potent to the glycoengineered B16F0 cell than to the Nphenylacetyl-D-mannosamine-treated 3T3 A31 cell. These results show the promise for developing useful melanoma immunotherapies based on vaccination against N-phenylacetyl GM3 followed by treatment with N-phenylacetyl-D-mannosamine.

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Cancer vaccines: An update with special focus on ganglioside antigens (Review)

Cited by 55 publications

References 0 publications

Efficient Metabolic Engineering of GM3 on Tumor Cells by N-Phenylacetyl-d-mannosamine

Efficient Metabolic Engineering of GM3 on Tumor Cells by N-Phenylacetyl-d-mannosamine

Tumour markers

Efficient glycoengineering of GM3 on melanoma cell and monoclonal antibody-mediated selective killing of the glycoengineered cancer cell

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