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

Summary 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...

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Veröffentlicht in:Clinical and experimental immunology 2018-07, Vol.193 (1), p.73-83
Hauptverfasser: Kvirkvelia, N., Chikadze, N., Makinde, J., McBride, J. D., Porakishvili, N., Hills, F. A., Martensen, P. M., Justesen, J., Delves, P. J., Lund, T., Roitt, I. M.
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Sprache:eng
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Zusammenfassung:Summary 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. We have explored whether the immunogenicity of vaccines containing an hCGb mutant (hCGbR68E) or hCGbCTP could be enhanced by coupling the immunogen to different carriers (KLH or Hsp70) using different cross‐linkers (EDC or GAD) and formulated with different adjuvants (RIBI or Montanide ISA720). The mutant provided a significantly better vaccine with significantly higher avidity than the hCGbCTP peptide. The highest antibody titres were obtained by linking it to Hsp70 carrier using GAD as cross‐linker and RIBI as adjuvant.
ISSN:0009-9104
1365-2249
DOI:10.1111/cei.13131