Immunotherapy Background and Overview

For many decades, the primary approaches to cancer treatment were surgery, chemotherapy, and radiation therapy.  Better targeted therapies such as monoclonal antibodies and other small molecule and biological drugs have been developed over the last 25 years.  More recently the exciting field known as immunotherapy has enabled the development of drugs that modulate the immune system to battle cancer.
We know that our bodies, through the function of our immune systems, are able to “cure” cancer.  It is now known that some number of cells in our bodies are becoming cancerous all the time.  These transformations are driven by many factors including genetics and environment.  Most of the time without us being consciously aware, these cells are destroyed and cleared by our immune system.  As our immune function declines with age, some cells are able to survive and eventually become tumors, either liquid or solid.  We also know that the tumors themselves have developed mechanisms to suppress immune cell function.  Such is the case with pediatric tumors as well adult cancers.
Considering this understanding, the field of immunotherapy tries to boost the ability of our immune cells to battle the cancer.  There are a number of methods that scientists have devised to induce our immune systems to battle cancer.  One of those approaches is known a Chimeric Antigen Receptor T-cell technology, better known by the acronym, CAR-T.
CAR-T therapy is a treatment where a patient’s T-cells, a type of immune cell, are removed from the body.  These cells are then modified in a laboratory through the advanced techniques of genetic engineering, and increased in number, and then infused back into the patient.  In many ways, this is the ultimate personalized medicine.  The specific genetic engineering is what makes the patient’s own T-cells even more powerful as a tumor fighter.  This genetic engineering causes a special receptor to be present on the surface of the T-cell.  This receptor is known as the CAR—the Chimeric Antigen Receptor.

While CAR-T treatment is complex, it has captured the attention of researchers and investors because it has produced remarkable responses in both children and adults suffering from specific types of liquid cancers, for whom other treatments had failed and for whom there were no other options. 
While CAR-T has shown spectacular results with some liquid tumors, to date there has not been any unequivocal positive results with solid tumors in humans.  ITUS believes that one of the primary reasons that CAR-T efficacy in solid tumors has been elusive is due to the lack of known antigens on the surface of solid tumor cells.  To understand this key attribute, it is useful to review key characteristics of the liquid tumor successes.
The specific tumors for which CAR-T has demonstrated effectiveness in humans, are all diseases of B-Cells (a type of white blood cell).  These are leukemias and lymphomas that result when B-cells become cancerous.  The FDA approved CAR-T therapies for B-cell tumors that target or attack a highly specific protein on B-cells known as CD-19.  It turns out that CD-19 is selective to B-cells and does not exist on other cells in the body.  Therefore, when a CAR-T is designed to attack this protein, it will not target other cells or organs in the body.   Unfortunately, the CAR-T therapy will kill healthy B-cells as well as the cancerous B-cells.  Luckily, with proper care and supplementation, the patient can survive without any B-cells.

Science and our Program

Recently, our collaborators demonstrated that ovary cells which have a protein receptor on their surface called the Follicle Stimulating Hormone Receptor (FSHR) can be targeted with CAR-T technology.  Studies also show that FSHR only exists on ovary cells in an adult female.  In addition, there exists a hormone called Follicle Stimulating Hormone (FSH) that binds exquisitely to the FSHR.  This hormone-receptor combination has evolved over millions of years to be highly selective.
The unique expression of FSHR on only one type of cell in an adult female is analogous to the CD-19 situation with B-cells.  Similarly, women can survive without their ovaries.  Therefore, we feel that CAR-T technology where the CAR is FSH and the antigen is FSHR, could be similar to the B-cell situation and our proprietary (patents filed) approach could be one of the first, if not the first, effective CAR-T therapy for a solid tumor.
Studies in vitro and in vivo (in animals) demonstrate excellent effectiveness of our CAR-T approach.  (Clinical Cancer Research, 23(2) January 15, 2017, 441-453).
Even more interesting is the fact that FSHR appears to be expressed on the surface of blood vessels in tumors of other types such as prostate, colon, lung, pancreatic and others.  This is an important point:  While FSHR does not exist on cells in healthy adults except for ovaries in women and testis in men, it does appear on blood vessels that nourish other tumors.  Therefore, should this therapy work for ovarian cancer patients, it may also work for multiple other cancers.


The markets for solid tumors is much larger than the markets for leukemias and lymphomas, especially B-cell cancers.  Therefore, we feel that the scope of opportunities for our CAR- T therapy is very large should we demonstrate efficacy in solid tumors.  Our first indication will be ovarian cancer, followed by other tumor types.