Investigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine

Porakishvili, N., Roitt, I.M., Lund, T., Delves, P.J., Justesen, J., Martensen, P., Chikadze, N. and Kvirkvelia, N. 2018. Investigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine. Clinical & Experimental Immunology. 193 (1), pp. 73-83. doi:10.1111/cei.13131

TitleInvestigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine
AuthorsPorakishvili, N., Roitt, I.M., Lund, T., Delves, P.J., Justesen, J., Martensen, P., Chikadze, N. and Kvirkvelia, N.
Abstract

Human chorionic gonadotrophin (hCG) and its β‐subunit (hCGβ) are tumour autocrine growth factors whose presence in the serum of cancer patients has been linked to poorer prognosis. Previous studies have shown that vaccines which target these molecules and/or the 37 amino acid C‐terminal hCGβ peptide (hCGβCTP) induce antibody responses in a majority of human recipients. Here we explored whether the immunogenicity of vaccines containing an hCGβ mutant (hCGβR68E, designed to eliminate cross‐reactivity with luteinizing hormone) or hCGβCTP could be enhanced by coupling the immunogen to different carriers [keyhole limpet haemocyanin (KLH) or heat shock protein 70 (Hsp70)] using different cross‐linkers [1‐ethyl‐3(3‐dimethylaminopropyl)carboiimide (EDC) or glutaraldehyde (GAD)] and formulated with different adjuvants (RIBI or Montanide ISA720). While there was little to choose between KLH and Hsp70 as carriers, their influence on the effectiveness of a vaccine containing the BAChCGβR68E mutant was less marked, presumably because, being a foreign species, this mutant protein itself might provide T helper epitopes. The mutant provided a significantly better vaccine than the hCGβCTP peptide irrespective of the carrier used, how it was cross‐linked to the carrier or which adjuvant was used when hCG was the target. Nonetheless, for use in humans where hCG is a tolerated self‐protein, the need for a carrier is of fundamental importance. Highest antibody titres were obtained by linking the BAChCGβR68E to Hsp70 as a carrier by GAD and using RIBI as the adjuvant, which also resulted in antibodies with significantly higher affinity than those elicited by hCGβCTP peptide vaccine. This makes this mutant vaccine a promising candidate for therapeutic studies in hCGβ‐positive cancer patients.

KeywordsHuman chorionic gonadotropin; cancer vaccine; Hsp70; adjuvant; B cell response
JournalClinical & Experimental Immunology
Journal citation193 (1), pp. 73-83
ISSN1365-2249
Year2018
PublisherWiley
Accepted author manuscriptInvestigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine.pdf
Digital Object Identifier (DOI)doi:10.1111/cei.13131
Publication dates
Published30 Mar 2018
Published online30 Mar 2018
Published in printJul 2018

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