Intelligent gel attacks cancer

This new injectable ‘biogel’ developed by researchers at the University of Montreal Hospital Research Centre (CRCHUM) is effective in delivering anti-cancer agents directly into cancerous tumours and killing them. The compound is made from chitosane, a biodegradable material extracted from the shells of crustaceans, to which gelling agents are added. The results of that study have been published recently in Biomaterials. CREDIT: CRCHUM

A new injectable ‘biogel’ is effective in delivering anti-cancer agents directly into cancerous tumours and killing them. This technology, developed by researchers at the University of Montreal Hospital Research Centre (CRCHUM), has already been successfully tested in the laboratory. If it works in patients, the therapy could one day revolutionize treatment for many forms of cancer.

Unlike ‘jello,’ the biogel is liquid at room temperature and gels at 37 degrees Celsius, human body temperature. “The strength of this biogel is that it is compatible with anti-cancer immune cells. It is used to encapsulate these cells and eventually administer them using a syringe or catheter into the tumour or directly beside it. Instead of injecting these cells or anti-cancer drugs throughout the entire body via the bloodstream, we can treat the cancer locally. We hope that this targeted approach will improve current immunotherapies,” said Réjean Lapointe, co-author of a study on the technology that was recently published in Biomaterials.

One form of immunotherapy involves treating cancer patients with anti-cancer immune cells. This is called adoptive cell therapy. These cells (T lymphocytes or T cells) are produced naturally by the body and have the ability to destroy cancer cells, but they are generally too weak and too few to eradicate the cancer alone. T cells are therefore cultivated in the laboratory, often the patient’s own cells, and then reinjected into the patient’s blood. While this form of immunotherapy has shown promising results in cases of advanced cancer, it is not always possible to generate enough T cells. Moreover, high doses of interleukin-2, a hormone added to maximize the therapy have a toxic effect.

With our technique, we only need to administer a few dozen million T cells, instead of the billions currently required. We can also administer compounds that ‘awaken’ the immune system to fight against cancer,” explained Lapointe, who is a researcher at the CRCHUM and professor at the University of Montreal.The recipe for this promising biogel was developed by Sophie Lerouge, a researcher at the CRCHUM and professor in the Department of Mechanical Engineering at the École de technologie supérieure. “The compound is made from chitosane, a biodegradable material extracted from the shells of crustaceans, to which gelling agents are added. The formulation is liquid at room temperature, which facilitates its injection, but quickly takes on a cohesive and resistant structure at 37 degrees. We also needed a hydrogel that was non-toxic for the body and provided excellent survival and growth of the encapsulated cells,” said the engineer. A real challenge for Lerouge’s team, who tested several formulations before arriving at this “intelligent” biogel.

The biogel was successfully tested in several in vitro models, including melanoma and kidney cancer. “The T lymphocytes in the gel are functional and can grow for two to three weeks, be released from the gel, and kill the cancerous cells,” explained Lapointe. The next step is to demonstrate the effectiveness of the biogel in animals and humans. If the trials are successful, this new approach could be added to current cancer therapies in a few years.

Monette et al. Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies. Biomaterials. 2016; 75: 237–249 [Abstract]


Nuclear medicine scan could identify who might benefit from aromatase inhibitor treatment

A new, noninvasive nuclear medicine test can be used to determine whether aromatase inhibitor treatment will be effective for specific cancer patients, according to a recent study reported in The Journal of Nuclear Medicine. The research shows that a PET scan with the ligand C-11-vorozole reliably detects aromatase in all body organs – demonstrating the value of its future use to pre-determine the effectiveness of the treatment for breast, ovarian, endometrial and lung cancer patients, potentially reducing unnecessary treatment costs and adverse effects.

Aromatase inhibitors are drugs that work by blocking the aromatase enzyme, which turns the androgen hormone into cancer-stimulating estrogen. They are widely used in the adjuvant treatment of breast cancer and other endocrine conditions. However, no quantitative, noninvasive studies had been done of the distribution and regulation of aromatase in living humans.

Anat Biegon, PhD, corresponding author of the study, explains, “This is the first study conducted in living human subjects that surveys the whole body, comparing healthy young and old men and women.”

For the study, 13 men and 20 women were injected intravenously with C-11-vorozole (111-296 MBq/subject), with PET data acquired over a 90-minute period. Each subject had four scans, two per day separated by two to six weeks. Brain and torso or pelvic scans were included. Young women were scanned at two discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned after pretreatment with a clinical dose of the aromatase inhibitor letrozole. Time-activity curves were obtained, and standardized uptake values (SUV) were calculated for major organs, including brain, heart, lungs, liver, kidneys, spleen, muscle, bone, and male and female reproductive organs. Organ and whole-body radiation exposures were calculated using OLINDA software.

The study shows for the first time that the body organ with the largest stable capacity for estrogen biosynthesis is the male brain, closely followed by the female brain. Aromatase availability is slightly but consistently higher in all organs in men relative to women, with the exception of the ovary. In addition, aromatase availability in the ovary is tightly linked to the ovulatory phase of the menstrual cycle in young women, with increased levels evident in one ovary/cycle around the time of ovulation. Also of interest is the finding that aging and cigarette smoke reduce aromatase availability in the brains of healthy men and women.

Dr. Biegon points out the significance of the study: “Research using in vitro methods indicates aromatase over expression is not limited to breast cancer and is evident in a considerable proportion of ovarian, endometrial, and lung tumors. This study provides methodological, baseline and dosimetry information supporting the use of PET and C-11 vorozole in the non-invasive identification of individuals with disparate disorders who may benefit from treatment with aromatase inhibitors.” She notes, “It also offers the ability to distinguish breast cancer patients who are not likely to benefit from this treatment, reducing unnecessary treatment costs and adverse effects. Finally, aromatase imaging can be used in monitoring efficacy of treatment with aromatase inhibitors and aid in the development of new drugs in this class.”

Another key finding relates to the differences between men and women. Dr. Biegon states, “Radiotracer uptake and the resultant radiation exposure can be sex-dependent and strongly modulated by hormonal status. Nuclear medicine procedures need to be adjusted for these factors when applied in women.”

Biegon et al. Aromatase Imaging with [N-Methyl-11C] Vorozole PET in Healthy Men and Women. J Nucl Med. 2015;56:580-585 EPub ahead of print. doi: 10.2967/jnumed.114.150383 [Abstract]