Antibody-drug conjugates (ADC) are effective antibody-based therapeutics for the treatment of cancer and hematological diseases. There is, however, an unmet medical need for the identification of novel targets. this is especially the case for the development and treatment of solid tumors.

Scientists at A&G Pharmaceutical and Precision Antibody have identified a prostaglandin F2 receptor negative regulator (PTGFRN) as an internalizing cancer cell target and isolated a proprietary internalizing antibody specific for the development of antibody-drug conjugates.

The companies centered their work on the identification of targets internalized and expressed on cancer cells by screening hybridoma libraries developed against cancer cell-surface antigens. These libraries include antibodies screened for their ability to bind, internalize, and deliver a cytotoxic payload to specific cancer cells. The results of their work was published in the January 2021 online edition of Plos One. [1]

This approach was used by A&G Pharmaceutical and Precision Antibody to characterize the mouse monoclonal antibody 33B7, an internalizing antibody, and identify its target by immunoprecipitation and mass spectrometry as PTGFRN.

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After target validation, 33B7 binding and target positivity were tested by flow cytometry and western blot analysis in several cancer cell lines. The researchers investigated the ability of 33B7, conjugated to saporin, to inhibit in vitro proliferation of PTFRN positive cell lines, as well as the 33B7 antibody-drug conjugates in vivo effect on tumor growth in athymic mice for several cancer types including head and neck cancers and spindle cell carcinoma.

The research team found that in vitro treatment PTGFRN-positive cancer cell lines with the 33B7-saporin antibody-drug conjugate inhibited their proliferation in a dose-dependent fashion. Furthermore, 33B7 conjugated to saporin was also able to block tumor growth in vivo in mouse xenografts when compared to a control ADC.

PTGFRN is a member of the cell surface tetraspanins family contributing to many key biological functions linked to adhesion, migration, and survival and shows promise as a therapeutic target.

For example, in glioblastoma PTGFRN is found to be overexpressed and to correlate with poor survival.[2]

The results demonstrated by the research team suggest that PTGFRN is a possible therapeutic target via an antibody-based approach for certain cancers.

“We are delighted to have identified PTFGRN as a promising internalizing cancer target that could increase the repertoire of therapeutic options for cancers with unmet needs. After developing diagnostic and therapeutic products for progranulin/GP88, it is exciting to contribute new cancer therapeutic options based on cell-surface protein,” noted Ginette Serrero, Ph.D., Chief Executive Officer of A&G Pharmaceutical.

“Knowing that our internalizing antibody development program led to the discovery of new targeted cancer therapy is rewarding,”  concluded Jun Hayashi, MD, President of Precision Antibody,

[1] Marquez J, Dong J, Dong C, Tian C, Serrero G. Identification of Prostaglandin F2 Receptor Negative Regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development. PLoS One. 2021 Jan 27;16(1):e0246197. doi: 10.1371/journal.pone.0246197. PMID: 33503070; PMCID: PMC7840024.
[2] Aguila B, Morris AB, Spina R, Bar E, Schraner J, Vinkler R, Sohn JW, Welford SM. The Ig superfamily protein PTGFRN coordinates survival signaling in glioblastoma multiforme. Cancer Lett. 2019 Oct 10;462:33-42. doi: 10.1016/j.canlet.2019.07.018. Epub 2019 Aug 1. PMID: 31377205; PMCID: PMC6705426.

Featured Image: Pharmaceutical scientific researchers analyzing liquid chromatography data; Pharmaceutical industry manufacturing laboratory Courtesy: © 2016 – 2021 Fotolia/Adobe. Used with permission.

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