Clinical and Immunological Effects of a Synthetic Beta-Human Chorionic-Gonadotropin Vaccine

Triozzi, Pierre L.; Gochnour, Diane; Martin, Elishba; Aldrich, Wayne; Powell, Jessica; Kim, J. A.; Young, D. C.; Lombardi, Jared

doi:10.3892/ijo.5.6.1447

Cited by 12 publications

(9 citation statements)

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“…The data obtained in the phase I clinical trial in 1994 (89) did not explain the mechanism of action of the vaccine. This mechanism was elucidated in 1998 by Kalantarov and Acevedo (90), who demonstrated that one of the three antibodies against the hCGβ‐carboxy‐terminal peptide that the vaccine elicits, has a direct dose‐related cytotoxicity at 37° C. At the time this review is being written, extensive phase II and phase III multicenter clinical trials, involving different types of cancer, are being performed in different locations in the United States.…”

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confidence: 89%

“…The investigators found that both native hCG and hCGβ inhibited Kaposi's sarcoma, while the hCGα did not have any effect (96). At that time, Dr. Gallo ought to have known the in vitro effects of hCG on the HIV virus, and the anti‐reverse transcriptase activity previously described by Bourinbaiar and his associates (87–89), since he supplied the HIV virus to those investigators in 1992. It is very possible that due to his heavy work load Dr. Gallo did not remember those basic studies.…”

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confidence: 98%

“…Since a prerequisite for a successful immunotherapeutic approach to cancer is the preferential expression by the malignant neoplasms of a membrane‐associated antigen, and taking into consideration that the embryonic and fetal cells, like cancer cells of every type and origin expressed membrane‐associated hCG in its different forms (10–13), it was obvious to test the WHO antifertility vaccine in different types of cancers. A phase I clinical trial of the anti‐hCG vaccine was done at the Ohio State University Comprehensive Cancer Center, the Arthur G. James Cancer Hospital and Research Institute, Columbus, Ohio, the city where the WHO vaccine for fertility control was developed (89). Twenty‐three patients with non‐trophoblastic cancers participated in this study.…”

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confidence: 99%

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Human chorionic gonadotropin (hCG), the hormone of life and death: a review

Acevedo

2002

J Exp Therapeutics

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confidence: 89%

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confidence: 98%

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confidence: 99%

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Human chorionic gonadotropin (hCG), the hormone of life and death: a review

Acevedo

2002

J Exp Therapeutics

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“…12 Clinical trials using anti-β-hCG cancer vaccines have been carried out in patients with epithelial, pancreatic, and colorectal cancer. 13 Thus, β-hCG constitutes a promising target for cancer immunotherapy and antitumor vaccine development. 14 Furthermore, antibodies against β-hCG and one type of hCG glycoform (hyperglycosylated hCG) have been shown to inhibit tumor cell growth and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Chemical Synthesis of the β-Subunit of Human Luteinizing (hLH) and Chorionic Gonadotropin (hCG) Glycoprotein Hormones

Fernández‐Tejada

Vadola

2014

J. Am. Chem. Soc.

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Human luteinizing hormone (hLH) and human chorionic gonadotropin (hCG) are human glycoprotein hormones each consisting of two subunits, an identical α-subunit and a unique β-subunit, that form noncovalent heterodimers. Structurally, β-hCG shares a high degree of sequence similarity with β-hLH, including a common N-glycosylation site at the N-terminus but differs mainly in the presence of an extended C-terminal portion incorporating four closely spaced O-linked glycans. These glycoproteins play important roles in reproduction and are used clinically in the treatment of infertility. In addition, the role of hCG as a tumor marker in a variety of cancers has also attracted significant interest for the development of cancer vaccines. In clinical applications, these hormones are administered as mixtures of glycoforms due to limitations of biological methods in producing homogeneous samples of these glycoproteins. Using the powerful tools of chemical synthesis, the work presented herein focuses on the highly convergent syntheses of homogeneous β-hLH and β-hCG bearing model glycans at all native glycosylation sites. Key steps in these syntheses include a successful double Lansbury glycosylation en route to the N-terminal fragment of β-hCG and the sequential installation of four O-linked glycosyl-amino acid cassettes into closely spaced O-glycosylation sites in a single, high-yielding solid-supported synthesis to access the C-terminal portion of the molecule. The final assembly of the individual glycopeptide fragments involved a stepwise native chemical ligation strategy to provide the longest and most complex human glycoprotein hormone (β-hCG) as well as its closely related homologue (β-hLH) as discrete glycoforms.

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“…In 1994, Triozzi et al published the results of a Phase I clinical trial of the WHO vaccine in cancer patients, which was performed at the Arthur G. James Cancer Hospital and Research Institute of the Ohio State University Comprehensive Cancer Center. 18 These investigators reported that, in the patients who demonstrated measurable antitumor activity, peripheral blood mononuclear cytotoxicity was not observed using standard 51 Cr-release assays, and there was no increase in natural killer cell activity. At the same time, in collaboration with the Department of Medicine and Pathology, Columbia University College of Physicians and Surgeons, New York, New York, and the AFRC Institute of Animal Physiology and Genetics Research, Cambridge Research Station, Bahraham, Cambridge, U.K., we published the results of the production and characterization of three mouse monoclonal antibodies (MoAbs) raised by the synthetic vaccine, which we designated CTP101, CTP102, and CTP103.…”

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confidence: 99%