Two Distinct Humanized Monoclonal Antibodies for Immunotherapy of Ovarian Cancer

Lee, Gregory

doi:10.4172/1948-5956.1000258

Cited by 8 publications

(19 citation statements)

References 35 publications

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“…In contrast, 100% homology in the corresponding CDR domains was maintained for the preservation of affinity and specificity of hGHR106 to the human GnRH receptor. Overall, the homology between mGHR106 and hGHR106 in the Fab regions was decreased to 93% and 89% for the heavy and light chains, respectively [22].…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, the bioequivalence between mGHR106 and hGHR106 have been clearly demonstrated through this humanization strategy [22]. Through binding inhibition studies, both hGHR106 and human or monkey derived N1-29 synthetic peptides of the GnRH receptor demonstrated significant dose-dependent inhibition to mGHR106 binding to the GnRH receptor, whereas mouse derived peptide revealed little to no inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, preclinical and clinical studies with humanized Mab may be the final proof to demonstrate the efficacy of hGHR106 in anti-cancer therapy, despite the fact that the slow-release long-acting GnRH peptide analogs or small organic molecules are also currently available for clinical studies [4,5,8,10,11,22,34,38,39].…”

Section: Discussionmentioning

confidence: 99%

“…mGHR106 was subsequently humanized (hGHR106) and evaluated through numerous biochemical and immunological studies [22]. The main objective of this study would be to determine if hGHR106 is substantially bioequivalent to mGHR106 and can serve as the alternative to decapeptide GnRH analogs in treating human cancer, as well as for other gynecologic indications [11].…”

Section: Anti-gnrh Receptor Monoclonal Antibodies First-in-class Gnrmentioning

confidence: 99%

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Anti-GnRH Receptor Monoclonal Antibodies, First-In-Class GnRH Analog

G¹,

Chow²,

Ch³

et al. 2015

Journal of Gynecology Research

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A monoclonal antibody (Mab) designated as GHR106 was generated against the extracellular domain (N1-29 synthetic peptide) of human gonadotropin releasing hormone (GnRH) receptor. It is a first-in-class GnRH analog and can serve as a drug candidate for potential applications in the treatment of human cancers and/or fertility regulations. Both Mabs in murine (mGHR106) or humanized (hGHR106) forms were shown to have comparable specificity and affinity to intact GnRH receptor on cancer cells or to N1-29 synthetic peptides from humans and monkeys. Similar to decapeptide GnRH analogs, both Mabs were shown to induce apoptosis to cultured cancer cells of various tissue origins, including those from the ovary, breast, prostate, and lung. However, both Mabs were also found to induce complement-dependent cytotoxicity (CDC) reaction for lysis of cancer cells, an immune property which is not shared by peptide analogs of GnRH. By using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), both GHR106 Mabs and the GnRH decapeptide antagonist, Antide, were shown to be bioequivalent in terms of their respective effects on genes involved in the proliferation and apoptosis of cancer cells. In addition, GHR106 Mabs have a much longer circulating half-life than GnRH peptide analogs (days versus hours). Based on the results of these studies, it can be concluded that both mGHR106 and hGHR106 are bioequivalent to the GnRH decapeptide antagonist, Antide, in many biological and functional properties. Therefore, hGHR106 can serve as a long-acting alternative to the current decapeptide GnRH antagonists for therapeutic treatments in the immunotherapy of human cancers, including those of gynecologic origin.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Anti-gnrh Receptor Monoclonal Antibodies First-in-class Gnrmentioning

confidence: 99%

See 2 more Smart Citations

Anti-GnRH Receptor Monoclonal Antibodies, First-In-Class GnRH Analog

G¹,

Chow²,

Ch³

et al. 2015

Journal of Gynecology Research

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“…Recently, humanized forms of RP215 have been successfully developed and shown to be bioequivalent to murine RP215 in terms of their relative biological actions in epitope specificity and affinity to cancer cells. Preclinical studies of humanized RP215 are being performed to see if it is qualified as antibody-based anti-cancer drug candidate for treatment of certain types of cancers in humans, especially for ovarian and lung cancer [75].…”

Section: Research and Development Of Rp215-based Anticancer Drugsmentioning

confidence: 99%

Cancerous Immunoglobulins in Cancer Immunology

2014

J Clin Cell Immunol

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The expression of immunoglobulins by cancer cells have been known for two decades. However, the mechanisms of action behind these cancerous immunoglobulins (cIgG) are not well understood and may be different from immunoglobulins secreted by normal B lymphocytes. Therefore, the structural and functional roles of cIgG have been actively investigated to resolve this mystery. A monoclonal antibody, RP215, was generated in 1987 and was shown to react with a carbohydrate-associated epitope localized mainly on the heavy chains of cIgG but not on normal immunoglobulins. The knowledge of cIgG has been greatly advanced by using RP215 as a unique probe. Not only was RP215 shown to act as an anti-cIgG to induce apoptosis of cultured cancer cells in vitro/in vivo, it was also shown to elicit complement-dependent cytotoxicity (CDC) reactions to trigger lysis of cancer cells. It has now been established that besides serving to preserve growth/proliferation of cancer cells by capturing growth factors from the human serum, cIgG may also interact with certain human serum proteins which may be harmful to cancer cells. Thus, the hypothesis of dual functional roles of cIgG can be adequately explained in cancer immunology. Furthermore, RP215 may also be used to target cancer cells with surface bound cIgG for development of antibodybased anti-cancer drugs, provided that bioequivalent humanized RP215 is available for preclinical and clinical studies of immunotherapy.

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Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer

Barrera

Hernandez-Martinez

Orozco‐Morales

et al. 2018

Cancer Immunol Immunother

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Polymorphonuclear-MDSC (PMN-MDSC) have emerged as an independent prognostic factor for survival in NSCLC. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone. We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3, CD3CD4 and CD3CD8), neutrophils (CD66b) and polymorphonuclear-MDSC (PMN-MDSC; CD66bCD11bCD15CD14-) as well as the concentration of 14 plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy donors (HD). In contrast to HD, NSCLC patients had a higher percentage of PMN-MDSC and neutrophils (P < 0.0001) but a lower percentage of CD3, CD3CD4 and CD3CD8 cells. PMN-MDSC% negatively correlated with the levels of IL1-β, IL-2, IL-27 and IL-29. Two groups of patients were identified according to the percentage of circulating PMN-MDSC. Patients with low PMN-MDSC (≤ 8%) had a better OS (22.1 months [95% CI 4.3-739.7]) than patients with high PMN-MDSC (9.3 months [95% CI 0-18.8]). OS was significantly different among groups of patients stratified by both PMN-MDSC% and cytokine levels. In sum, our findings provide evidence suggesting that PMN-MDSC% in conjunction with the levels IL-1β, IL-27, and IL-29 could be a useful strategy to identify groups of patients with potentially unfavorable prognoses.

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Two Distinct Humanized Monoclonal Antibodies for Immunotherapy of Ovarian Cancer

Cited by 8 publications

References 35 publications

Anti-GnRH Receptor Monoclonal Antibodies, First-In-Class GnRH Analog

Anti-GnRH Receptor Monoclonal Antibodies, First-In-Class GnRH Analog

Cancerous Immunoglobulins in Cancer Immunology

Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer

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