Cancer
Immunolight has created what we believe will be a paradigm shift in the treatment of cancer. If you got cancer 40 years ago there were 3 primary treatment options – surgery, chemo, and radiation. Today there have clearly been advances in all three, but cancer remains a very, very significant medical, emotional and financial plague on society. Our highest priority at Immunolight is to translate innovations in energy conversion, our core technology, into developing new possibilities for targeted therapies to treat cancer.
Our lead approach to this paradigm shift is based on an ancient drug, psoralen. Psoralen’s root can be traced to the ancient Egyptians, who recognized it was activated by UV light and used it as a treatment for skin disorders.
In the era of modern medicine, psoralen has been used as a front line treatment for refractory psoriasis. In that application, patients took the drug orally and stood in a UV light box. The psoralen that was in the psoriatic lesion was activated by the light hitting the skin and in many cases induced a robust, lasting effect.
Psoralen has also been used in a procedure called photopheresis, developed for the treatment of Cutaneous T Cell Lymphoma, a malignancy of the blood. In that application, because UV light can’t penetrate tissue, blood cells were removed from the patient, exposed to psoralen and UV light, and reinfused back to the patient. Although only a tiny percent of diseased cells were directly treated outside the body, robust systemic clinical effects were seen, suggesting some sort of amplification of an immune response may be occurring. Although the exact mechanism of how this happens has been studied extensively for over 20 years, it remains elusive.
Immunolight Method
In our lead application for the treatment of solid tumors, we seek to activate psoralen inside the tumor in an attempt to generate an immune reaction against the tumor, and possibly systemically to other areas. In order to do this, because UV light can’t penetrate tissue it must be generated inside the tumor. To accomplish this we innovated tiny particles that can absorb energies that are capable of penetrating tissues (such as low dose X ray), and convert them into UV light, which in turn can activate the psoralen inside the tumor. Once activated, the psoralen kills the cell in a pathway that generates the immune response seen with the previous psoralen based applications.
It is our hope this therapy will represent an alternative treatment for cancer whose hallmark will be a non-invasive, immune based treatment that does not involve the introduction of cytotoxic agents used in conventional chemotherapy, thus eliminating the devastating, life altering side effects of current therapies.
Cell Studies
After the completion of extensive analytical and bench-top assessments of numerous energy converter chemistries, the performance of the system was tested in cancer cells.
Cancer cells were chosen from typical human and mouse cell lines and included cancer of the skin (melanoma), multiple variants of breast cancer, prostate cancer, airway cancer and colorectal cancer. In addition, comparison tests were done in normal cells.
Multiple types of tests were conducted to look at the viability (WST) and survivability (Clonogenic) of cells after treatment, as well as the mechanistic pathway of death as measured by flow cytometry or western blot.
Displayed below are several energy converter combinations, tested against multiple X ray conditions, showing consistent reduction in cell survival as compared to controls (no drug).
In addition to the viability or survival of the cell, the pathway of death was also studied. Specifically, markers for apoptosis, a programmed cell death that may be associated with the body’s ability to mount an immune response were looked at in multiple cell lines.
Displayed below are results looking for cleaved PARP, a sign of DNA damage to a cell. In particular, note that for the breast cancer cell types (BT474 and 4T1) there is a treatment effect (psoralen plus energy transducer), but in normal cells (HFF), no cleave PARP signal is detected, suggesting the treatment effects selects for cancer cells over normal cells.
Animal Data
After completion of successful studies in multiple cell lines, two animal rodent studies were conducted to demonstrate safety and feasibility in-vivo. The studies were reviewed and approved by an accredited Institutional Animal Care and Use Committee (IACUC).
A very fast growing, highly metastatic breast cancer was chosen as the cell line of choice. Approximately 500,000 cells were injected below the skin of the thigh and allowed to grow until it reached a small measurable volume.
At that time treatments were started. The psoralen was mixed with the energy converters and directly injected into the tumor. The injection was followed by a low level X ray. The treatment was conducted 3 times a week for up to 4-6 weeks. At regular intervals the tumor volume and body weight were measured.
The representative treatment groups were as follows:
Normal saline
X-Ray and Psoralen only
X-Ray and Energy Converter only
X-Ray and Energy Converter and Psoralen
Additionally, body weight was measured as an indicator of gross systemic toxicity – weight loss can be an indication of acute toxicity.
Displayed below are the weight data collected during the study conduct. Each line represents the average weight of each group that was treated in the study. Note that all the groups have similar weight profiles, and that in particular the groups under treatment did not lose weight compared to the (untreated) controls, suggesting no significant toxicity was caused by the treatment.