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Body Wars: Designing Antibodies to Fight Cancer

March 20, 2015

Body Wars: Designing Antibodies to Fight Cancer

Cytotoxic T cells (CTLs) are natural-born killers. They are the immune system’s “boots on the ground,” seeking out and destroying cells that are infected or have become cancerous.  These CD8 T cells are trained to recognize foreign (i.e. non-self) antigens, which are molecular tags that allow them to “see the enemy” and kill off the intruders.

Unfortunately, cancer cells deploy various countermeasures, including camouflage and means of suppressing the anti-tumor immune response.  One of the most effective of these subversive countermeasures is triggering the PD-1 receptor on CTLs.  This effectively gives the CD8 cell the “hold your fire” command and stops the immunological attack in its tracks. Thanks to advances in immunotherapy, scientists can now design antibodies to aid our immune system’s fight against cancer.  In fact, monoclonal antibodies that block this PD-1 “off-switch” are proving to be powerful new tools, effective in a subset of patients across a wide range of tumor types. Identifying those patients who will respond to these agents is a top priority in oncology today.

Predicting the Success of Immunotherapy

Now a collaborative arrangement that includes the University of California, Los Angeles (UCLA), drug developer OncoSec, and PerkinElmer may help researchers  find  promising new technologies  to identify  the cellular and molecular signature of those patients, who will respond to anti-PD1 blocking agents.  The technology uses a quantitative pathology-imaging research platform called Vectra® developed by PerkinElmer. Paired with the company’s Opal multiplex tissue staining system, the Vectra platform measures the expressions and characteristics of proteins on tissue. It then stains multiple biomarkers within a single tissue region using a method called immunohistochemistry (IHC). This platform delivers an image of the intact tissue, simultaneously stained with multiple biomarkers, which preserves critical information about the relationships between cells and to other anatomic structures.  This capability offers an important advantage over alternative techniques such as flow cytometry, which require disassociation of the tissue, resulting in the loss of this critical structural information.

The advantages of this technology are not lost on researchers. They are using this new multiparametric immunohistochemistry (IHC) analysis platform to expand upon earlier research into why some cancer patients respond to a type of mAbs called PD-1 checkpoint inhibitors while others do not.

High Hopes for New Multi-parametric IHC Analysis Platform

Enter the Vectra platform. UCLA researchers are currently employing the intelligent analysis capabilities of the Vectra platform to examine earlier research  into understanding which patients may or may not naturally respond to PD-1 targeting drugs. OncoSec believes there is a significant unmet medical need to develop combination therapies for those patients. OncoSec is working on an investigational agent called ImmunoPulse to deliver a protein directly into tumors to enhance the immune system and convert non-responders to responders.

“The analytical needs of both UCLA and OncoSec are well aligned with our unique technical capabilities,” says Brian Kim, President, Life Sciences & Technology, PerkinElmer. “This project complements our focus on enabling research to reveal the intricacies of immuno-oncologic interactions. Through this work with UCLA and OncoSec, we think we can make a meaningful contribution toward assisting researchers in improving outcomes for patients.”

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