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COI Can: World Cancer Day

A reporter recently asked us whether there needed to be more drug development in cancer, since there already seemed to be so many companies and recent breakthroughs in the cancer field. There are 8.8 million people who die from cancer worldwide every year and remains the second leading cause of death. There are obvious unmet medical needs and important new discoveries and treatments that need to be made. For COI, February 4 is a day when we reflect on what we can do to find better treatments to fight cancer.

COI Can: Modulate the Immune System to Develop Cancer Fighting Therapies

Most cancers grow and spread throughout the body by developing ways to avoid detection by the body’s natural cancer regulators, the immune system. One of the methods for treating cancer is to help the immune system find and destroy the evasive cancer cells.

Exposing Tumor Cells
PDI Therapeutics is developing a therapeutic that could improve specific immune responses against tumors. Tumor cells have developed a mechanism that allows them to evade the function of a group of immune cells called natural killer cells (NK cells).  PDI Therapeutics is developing antibodies that targets this tumor mediated evasion and, in doing so, would allow the NK cells to find and kill cancer cells.  The company is in the process of optimizing the antibody drug candidates for clinical development.

Optimizing Anti-tumor Activity
Another approach to killing cancer cells is to enhance the existing features of the immune system. Immune cells can become activated by interacting with molecules in their environment, known as cytokines.

Using their scalable and tunable synthetic biology platform, Synthorx is optimizing a cytokine, called IL-2 (aldesleukin).  IL-2 was approved in the early 90’s as the first “immune-oncology” drug before the term was coined and before its molecular mechanisms were fully understood. Known as a very toxic drug, it demonstrated cures in some metastatic melanoma and renal cell cancer patients which was unheard of at that time. While a potent drug, IL-2 has multiple functions when bound to different receptors.  Some of these functions can have toxic, unwanted effects.  The Synthorin™ engineered at Synthorx is designed to eliminate the toxicity of native IL-2 by tuning to specifically bind to and stimulate the anti-tumor activity in immune cells.  This therapy will work on its own, but importantly, it will be combinable with other immune-oncology regimens for a variety of cancers including renal cell carcinoma, melanoma, non-small cell lung cancer, and bladder cancer.

Stimulating Anti-tumor Immune Cells
Adanate is a new COI company that is exploiting a family of proteins, called leukocyte immunoglobulin-like receptor B (LILRBs), which are involved in preventing an appropriate host response to cancer or infectious disease.  In cancer, LILRBs work by dampening the immune response and creating an immunosuppressive environment within solid tumors.

Adanate has generated numerous antibody drug candidates that can block the activity and function of LILRBs.  The antibodies work by converting a type of white blood cell, macrophages, from one activation stage (M2) to another (M1). M1 macrophages have the potential to kill cancer cells.  The antibodies can also generate an appropriate T-cell response against the cancer which can also lead to tumor shrinkage.  The company plans to advance these new drug candidates towards clinical development by the end of the year.

Targeting with Tumor-killing Drugs
Utilizing antibodies, Fortis Therapeutics is tackling cancer by directly delivering drugs to the inside of cancer cells.  Antibodies are the immune system’s way of ‘seeing’ foreign invaders, such as bacteria, or parts of our own cells that may have gone awry, like cells do when they become cancerous. Taking advantage of this specific ‘sight,’ Fortis is designing an antibody drug conjugate (ADC), which is an antibody linked to a cytotoxic drug.

Fortis’ ADC can target the cancer cell, via a protein called CD46, and be transported inside where the drug can release its cell-killing effects. BioSpace recently had a chat with Fortis CEO, Jay Lichter, Ph.D., to get a better understanding of how this ADC works.

“[CD46] is primarily involved in getting nutrients from the microtumor environment to feed the tumor and it does this by a mechanism called chemocytosis, where little vesicles are formed and suck micronutrients into the cell,” said Lichter. “The antibody-conjugate binds to this target and will be actively transported in due to the inherent mechanism of this target.”

COI Can: Improve Surgery with a Real-Time Cancer Illuminator

While innovative cancer therapeutics have increased treatment options for patients, there has been limited progress in improving care within the operating room. To date, surgeons have relied primarily on their eyes and hands to determine the boundaries between cancerous and noncancerous tissue.  These techniques can be ambiguous and subjective, and results can only be confirmed days or weeks later after removed tissue is examined by a pathologist.

Avelas Biosciences is working to improve surgeons’ ability to completely remove the cancer during the first surgery by developing a real-time “cancer illuminator,” called AVB-620, which is designed to enable surgeons to distinguish tumor from normal tissue. The goal is to provide the necessary real-time information needed by surgeons to visualize and excise the cancerous tissue while they operate and help avoid the need for additional surgeries.

Last October COI featured Avelas’ technology for Breast Cancer Awareness Month and, just recently, the company announced completion of Period 1 patient enrollment for the  Phase 2 Study of AVB-620.  Avelas CEO, Carmine Stengone, had this to say about the trial and technology:

“This study is designed to confirm the findings of our Phase 1b study, which demonstrated that AVB-620 generates fluorescent signals that can distinguish breast cancer from adjacent non-cancerous tissue. We believe this technology has the potential to reduce the number of repeat surgeries from incomplete initial resections, potentially resulting in substantial cost savings and superior outcomes for patients.”

Identifying and working to eliminate critical unmet medical needs, such as improved therapeutics and tools for treating cancer, is a priority at COI.  On World Cancer Day we are all reminded of the burden these diseases can carry, but this year we can also be inspired to keep working toward innovative solutions in hopes of one day finding a cure.

Learn more about the worldwide efforts of individuals and groups who are taking action in the fight against cancer by visiting www.worldcancerday.org