HN125 new anti-OVCA therapy

This information is the result of preliminary research that will take years to trickle down to benefit any of us. Nevertheless, it is pretty exciting for me to find this as I am still somewhat of a "chemophobe."

For those of you who get blurry-eyed when reading scientific research, let me break it down for you:

Basically, CA-125 (aka MUC16) and is a protein found on the surface of epithelial OVCA that is not only a tumor marker but ALSO an "antigen" (another word for a protein that causes an antibody response--like an allergic reaction) that actually PROMOTES ovarian cancer.

Other research [which I can post but it will make your head spin] has shown that when MUC16 is blocked, there is much less platinum resistance of OVCA and more sensitivity to other chemo agents also. So that is the reason why this kind of research is being done in the first place.

A new therapy called "HN125" has been developed which targets those cancer cells that have CA-125 (MUC16) on them and basically kills them ("...strong...cytotoxicity against MUC16 positive cancer cells in vitro"). "In vitro" means the therapy was used outside the body on cancer cell lines where therapeutic agents are always used first before they are tested inside the body--first in mice, then in humans.

Think of this as similar to an allergy shot for some people with OVC--I think it only goes after the epithelial OVCAs. The key to this therapy is having a functioning immune system. So file it under "biological therapy" in your brain and pray that it gets "fast-tracked."

See below for the article on HN125:

J Cancer. 2011;2:280-91. Epub 2011 May 16.
HN125: A Novel Immunoadhesin Targeting MUC16 with Potential for Cancer Therapy.
Xiang X, Feng M, Felder M, Connor JP, Man YG, Patankar MS, Ho M.
Source1. Antibody Therapy Unit, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;

Abstract
BACKGROUND: The mucin MUC16 expresses the repeating peptide epitope CA125 that has been known for decades to be a well-validated cancer marker that is overexpressed on the cell surface of ovarian cancers and other malignant tumors. In spite of recent efforts to make mouse monoclonal antibodies to MUC16 to treat ovarian cancer, a human monoclonal antibody against this mucin has not been described. MUC16 interacts with mesothelin, a protein that mediates heterotypic cancer cell adhesion, indicating that MUC16 and mesothelin play an important role in the peritoneal implantation and metastasis of ovarian tumors. Therefore, a suitable candidate for therapeutic targeting of MUC16 would functionally block the interaction of MUC16 and mesothelin.

METHODOLOGY/PRINCIPAL FINDINGS: Here we report the generation of a novel immunoadhesin, HN125, against MUC16 that consists of a functional MUC16 binding domain of mesothelin (IAB) and the Fc portion of a human antibody IgG1. The yield for purified HN125 proteins is over 100 µg/mL of HEK-293 culture supernatant. We show that HN125 has high and specific affinity for MUC16-expressing cancer cells by flow cytometry and immunohistochemistry. HN125 has the ability to disrupt the heterotypic cancer cell adhesion mediated by the MUC16-mesothelin interaction. Moreover, it elicits strong antibody-dependent cell mediated cytotoxicity against MUC16-positive cancer cells in vitro.

CONCLUSION/SIGNIFICANCE: This report describes a novel human immunotherapeutic agent highly specific for MUC16 with potential for treating ovarian cancer and other MUC16-expressing tumors. Because of its lower immunogenicity in patients, a fully human protein is the most desirable format for clinical applications. We believe that the methods developed here may apply to the generation of other tumor-targeting immunoadhesins when it is difficult to obtain a human monoclonal antibody to a given antigen for clinical applications. The resultant immunoadhesins can have advantages usually found in monoclonal antibodies such as ease of purification, high binding affinity and effector functions.