Reduction of spontaneous metastases through induction of carbohydrate cross-reactive apoptotic antibodies.
The selective targeting of tumor-associated carbohydrate Ags by the induction of serum Abs that trigger apoptosis of tumor cells as a means to reduce circulating tumor cells and micrometastases would be an advantage in cancer vaccine development. Some plant lectins like Griffonia simplicifolia lectin I and wheat germ agglutinin mediate the apoptosis of tumor cells. We investigated the possibility of using these lectins as templates to select peptide mimotopes of tumor-associated carbohydrate Ags as immunogens to generate cross-reactive Abs capable of mediating apoptosis of tumor cells. In this study, we show that immunization with a mimotope selected based on its reactivity with Griffonia simplicifolia lectin I and wheat germ agglutinin induced serum IgM Abs in mice that mediated the apoptosis of murine 4T1 and human MCF7 cell lines in vitro, paralleling the apoptotic activity of the lectins. Vaccine-induced anti-carbohydrate Abs reduced the outgrowth of micrometastases in the 4T1 spontaneous tumor model, significantly increasing survival time of tumor-bearing animals. This finding parallels suggestions that carbohydrate-reactive IgM with apoptotic activity may have merit in the adjuvant setting if the right carbohydrate-associated targets are identified.
Monzavi-Karbassi
Behjatolah
B
Arkansas Cancer Research Center and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, 72205, USA.
Artaud
Cecile
C
Jousheghany
Fariba
F
Hennings
Leah
L
Carcel-Trullols
Jaime
J
Shaaf
Saeid
S
Korourian
Soheila
S
Kieber-Emmons
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis* / Q000097:blood / Q000627:therapeutic use*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000235:genetics / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D045744:Cell Line, Tumor; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014909:Wheat Germ Agglutinins / Q000494:pharmacology
D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014909:Wheat Germ Agglutinins