Anti-p16 antibodies for pathological cancer diagnosis

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Diagnosing pathologic cancer is often a challenge, even for the most skilled clinicians. Many forms of cancer do not have visible symptoms until the infection has progressed too far to be treated effectively.

Monoclonal antibodies emerge as a tool for everything from cancer diagnosis to treatment and even radiation therapy or chemotherapy in targeted areas of the body. Recently, researchers cloned a new anti-p16 antibody that could become a valuable new tool for pathological cancer diagnosis.

What are monoclonal antibodies?


To understand the new anti-p16 antibody, we first need to understand monoclonal antibodies and how they are applied to the diagnosis and treatment of cancer.

In a healthy body, the immune system responds to any intrusive agent – bacteria, viruses, or malignant cancer cells – by attaching an antibody to the intruder. From there, the immune system can work to destroy the invading cells. With a diagnosis of cancer, the body often cannot keep up with the rapid production of malignant cells.

Monoclonal antibodies replace natural antibodies. In the treatment of cancer, they bind to antigens on the surface of cancer cells. It is easy to direct these antibodies because cancer cells have more antigens than healthy cells.

Monoclonal antibodies can handle a variety of tasks related to cancer diagnosis and treatment, including:

Detect cancer cells and report them to the immune system.

Block the growth of cancer cells, preventing the growth of blood vessels and destroying the membranes of cancer cells.

Attack cancer cells directly.

Delivery radiotherapy or chemotherapy treatments.


This is by no means an exhaustive list. Researchers are discovering new applications for monoclonal antibodies every year – and new antibodies to work with.

Identification of p16 INK4a proteins


The p16 INK4a protein is one of many proteins all belonging to the family of cyclin dependent kinase (CKI) inhibitors. Specifically, it acts as an inhibitor of CDK4 and CKD6 proteins and plays a role in DNA repair, cell senescence and apoptosis. When functional, the p16 INK4a protein acts as a tumor suppressor. It can easily become carcinogenic if it mutates or contains any kind of genetic defect, such as homozygous deletions or nonsense mutations.

Diagnosticians will typically find p16 INK4a mutations in cell lines derived from tumors, but they have also been found in a variety of different cancers, including:

Melanoma

Gliomas

Esophageal cancer

Pancreatic cancer

Lung cancer

Urinary bladder cancer

Currently, the E6H4 protein is the most commonly used anti-p16 clone for cancer diagnosis, but it is not the only protein applied for this task. Studies have also evaluated the following protein clones:

16P04

JC8

16P07

G175-405

K5334

K5336

7962


The 16P04 and JC8 clones obtained better results than the E6H4 protein on several criteria, exhibiting higher sensitivity, better specificity and a more precise positive predictive value. The other clones did not perform as well but still have various applications within the diagnostic community.

A new anti-p16 antibody, which exists as a clone of BC42, has higher sensitivity and staining specificity than proteins previously used for the same diagnostics.

How can an anti-p16 antibody help?


The anti-p16 INK4a BC42 antibody clone has been extensively tested in various examples of gynecological pathology compared to the more standard E6H4 clone which has previously been used to diagnose cancers of the female reproductive system.

In the case of things like vulvar intraepithelial neoplasia (VIN), the diagnosis can go two different ways depending on the expression of the gene – p53 or p16. Having an anti-p16 antibody that can differentiate between the two pathogenic pathways can make the diagnosis easier. It can also determine the difference between a low-grade squamous intraepithelial lesion (SIL) (VIN1) and a high-grade SIL (VIN 2/3).

In the same study, examining neoplastic lesions of the uterus, anti-p16 antibody found expression of p16 INK4a in 80% of stained endometrial carcinomas, and the remaining cases showed positivity of 100 %. The original E6H4 clone as well as the new anti-p16 BC42 antibody show great precision for this particular type of diagnosis.

The introduction of anti-p16 antibodies offers diagnosticians a new avenue to explore when previous techniques could ignore malignant cells. Combining this data with artificial intelligence and machine learning systems can create a system capable of diagnosing cancer with a very small margin of error. Right now, Google researchers are working with an algorithm called Lymph Node Assistant (LYNA) that can look at images of healthy and diseased lymph nodes and determine if cancer cells are present. In some cases, the algorithm was more precise than that of professional radiologists.

The future of pathological cancer diagnosis


Ideally, a cure for cancer will replace the need for all of these advanced diagnostic tools. Yet as it stands, the anti-p16 INK4a antibody can make a huge difference in the speed and accuracy of cancer diagnosis. With most cancers, early detection increases the chances of survival and remission, so these tools could save countless lives in the long run.

The anti-p16 antibody does not replace existing diagnostic tools, but rather a tool that will help augment and support existing methods to give oncologists the tools to save lives.


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