Dec
07
2019

The Use Of Oncolytic Viruses For Cancer Treatment

In the first place, preliminary experiments indicate that the use of oncolytic viruses for cancer treatment may become a reality. There are several lines of research that point to the fact that oncolytic viruses can make a difference in treating incurable cancer patients.

Notably, Canadian researchers had reported in 2011 that oncolytic viruses created by genetically modifying smallpox vaccine viruses would enter tumor cells of patients, but not damage normal cells. Specifically, a high percentage of the end stage patients responded with tumor regression.

Shortly after Mayo Clinic physicians were desperate when two patients with end stage multiple myeloma, a vicious bone tumor, did not respond to chemotherapy. Significantly, they tried something unconventional: high doses of the measles vaccine in an attempt to stimulate the immune system. Here is an overview from 2014 that shows that many different cancers respond to various immunological approaches.

Study from Holland regarding end stage melanoma patients

Here is a small human study involving end-stage melanoma patients treated with the oncolytic virus T-VEC combined with pembrolizumab (Keytruda). It is important to realize that Keytruda helps to reactivate a T-cell response to the cancer cells. In this case the cancer cells absorb the oncolytic virus (T-VEC), but it leaves normal cells alone. Inside the cancer cells the oncolytic virus multiplies and destroys the cancer cells. In this 2017 study 21 patients with terminal, nonresectable melanoma received treatment with T-VEC and Keytruda. Specifically, 62% of the patients showed an objective response to the treatment. Moreover, 33% fulfilled the criteria of an immune-related response. In the past terminal patients like these had a 0% response to radiotherapy or chemotherapy.

History of research about oncolytic viruses

To begin with, in 1912 rabies virus treatment against cervical carcinoma was a first attempt to treat cancer. Researchers conducted many experiments between 1950 and 1970 with wild type or naturally attenuated viruses. This included, for example, hepatitis A and B viruses. In 1991 cancer researchers developed the concept of genetically engineered oncolytic viruses. Today cancer researchers know that the protection mechanisms in most cancer cells have deficiencies. This involves the interferon‐beta signal pathway. Having said this, there is an opportunity to let oncolytic viruses destroy cancer cells, while normal cells stay unaffected. An oncolytic virus that cancer experts use in human cancers is the genetically engineered herpes simplex virus type I (HSV‐1). Others that cancer researchers developed have strange names like T‐Vec, G47∆, JX594, CG0070 and Reolysin.

Various cancers that researchers treated with oncolytic viruses

Here are a few examples of cancers where researchers used oncolytic viruses to exert a significant therapeutic effect.

Glioblastoma

Glioblastoma is a deadly form of a brain tumor, which has a high rate of mortality. Researchers have investigated new avenues to treat this cancer. Researchers tested the genetically engineered dendritic vaccine. Initial clinical trials showed significant effectiveness compared to non-treated controls. In a large phase 3 clinical trial 331 patients with newly diagnosed glioblastoma received treatment at the time of neurosurgery with dendritic cell vaccine. 30.2% of the patients were still alive and doing well after 3 1/3 years. Without the added vaccination procedure all of these patients would have died in the past because of the aggressiveness of the glioblastoma.

Multiple myeloma

Researchers could cure multiple myeloma and other cancers by using the measles vaccine. Here is a report by the popular press about two women who had multiple myeloma. One woman got cured by high doses of a measles vaccine. The other women experienced some relief, but did not survive.

This publication explains that oncolytic viral therapy of cancer is a lot more complicated than originally thought.

Prostate cancer

Researchers found that vaccines against prostate cancer were effective with the combination of oncolytic virus therapy with regular anti-cancer treatments. But oncolytic virus therapy alone has a poorer prognosis than a combination of chemotherapy or radiotherapy with oncolytic virus therapy.

Cervical cancer

The high-risk HPV16 strain most often causes cervical cancer. The HPV (human papilloma virus) vaccine targets patients with previous exposure to HPV16. However, researchers have noticed that in some cases a phenomenon called the “HPV immune escape” has allowed in some vaccinated women to still develop cervical cancer. Now a group of researchers are investigating how the vaccine could be improved by finding out how the immune system is being tricked in these cases by the HPV virus to bypass the antibodies of the vaccine.

Pancreatic cancer

This cancer is very difficult to detect in the early stages, and as a result the outlook for chemotherapy or radiotherapy is extremely poor. Researchers have used several approaches as an alternative to conventional therapy. Immunotherapy is an option. Mayo clinic researchers have already announced that the measles vaccine approach will likely be applicable to pancreatic cancer treatment as well in the near future. However, other clinical trials are on the way to use alternative vaccination procedures.

Neuroblastoma, glioma and melanoma

This link shows that the FDA has accepted engineered oncolytic herpes virus (engineered to secrete GM-CSF) as a treatment against melanoma. Other approaches with engineered bacteria can affect neuroblastoma and glioma.

Survival data using oncolytic viruses for cancer treatment

Cancer researchers have completed a number of smaller clinical trials at this point. One of them describes end stage melanoma (stage III and IV) where the only treatment was with the oncolytic virus T‐Vec. The overall response rate compared to the control, which was only 5.7%, the experimental group with T-Vec was 26.4%. This is considered a good response rate given that we are dealing with end stage melanoma patients.

Mechanism of how oncolytic viruses stimulate the immune system to overcome various cancers

As mentioned above oncolytic viruses multiply in the cancer, once they have been incorporated. This leads to cancer cell death. It exposes the dead cancer tissue to the immune system. What helps in the process is that inhibitory proteins from the cancer cells that used to inhibit the immune system are no longer provided by the dead cancer cells. The end result is that the immune system mounts a formidable response against the cancer cells through killer T cells. This immune response also affects remote metastases of the same histological cancer type. This review article summarizes how oncolytic viruses work for cancer cell destruction and how this method can be combined with other treatment modalities.

The Use Of Oncolytic Viruses For Cancer Treatment

The Use Of Oncolytic Viruses For Cancer Treatment

Conclusion

Currently various cancer centers are involved with clinical trials in humans to test the power of oncolytic viruses. What cancer researchers have learnt is that oncolytic viruses are a useful tool to kill cancer cells. But the immune system of cancer patients is in a suppressed state. Pembrolizumab (Keytruda) is a medication that will stimulate the immune system by stimulating killer T cells to destroy cancer cells. The combined effect of killing cancer cells with oncolytic viruses and stimulating the immune system is the big news. This has been the breakthrough that cancer researchers have been waiting for. Now several clinical trials are on the way where survival rates for cancer patients given the new combination therapy are assessed.

Oncolytic virus therapy here to stay

It is a treatment which is no longer a thought model with animal experiments. Well known medical centers are using it in patients, and as the results become more obvious, it will very likely become a new treatment modality for cancer.

Mar
25
2015

Can Cancer Be Beaten?

For decades we have been indoctrinated that cancer can be beaten, but only marginal progress has been achieved with respect to effective cancer treatment modalities. So, we have become accustomed to be negative about the answer to the question “can cancer be beaten?” I like to propose that the answer is a resounding “yes”, but what has already been achieved needs to be further refined.

We know for a long time that there are distinct differences between the glycolytic cancer cell metabolism (“Warburg effect”) and the aerobic metabolism of normal cells.

In recent years the introduction of photochemical sensitizers followed by laser activation has made significant inroads regarding cancer treatment successes.

Animal experiments

Using a mouse model Ref.1 reported about the use of several photosensitizers to treat Ehrlich ascites carcinoma. The most effective substance was Hypericin, which is derived from Hypericum perforatum, also known as St. John’s wort. It showed the highest intracellular accumulation within the tumor cells, and the survival curves were the best with 25% cures after just one photodynamic treatment and a significant delay of mortality in the remainder of the animals. The control animals lived only 25 days on average, the Hypericin pretreated and photodynamic therapy treated animals lived about 70 days with the cured ones still being tumor free at 120 days.

Experiments like these have taught the medical profession that the type of photosensitive agent (e.g. Hypericin) matters, particularly how well it is taken up by the tumor. The other important factor is the absorption pattern of the agent, as the choice of laser light will determine how good a match there is between the wavelength of the laser and the inherent peak excitation of the agent (absorption spectrum).

Laser treatment of a group of melanoma patients

In Ref. 2 Dr. Weber described a report by Dr. M.A. Kaplan that was presented at the 2008 international laser conference in Helsinki. 76 patients with metastasizing melanomas were treated with Chlorin E6 (a natural photo-sensitizer) and intravenous laser for activation. 45% had reduced pain and improved life quality, in 22% of the cases lymph nodes with metastases either disappeared or became smaller; in 33% the metastases stopped spreading for 6 to 12 months.

Photodynamic therapy of a patient with duodenal cancer and liver metastases 

Dr. Michael Weber who is a specialist for internal medicine and the inventor of the Weber low-dose laser machine has treated cancer patients with photodynamic therapy (PDT) where his laser machine was used. I have described the Weber low-dose laser system before in a previous blog with uses for pain control.

One such cancer case was a female patient with a duodenal cancer (described in Ref.2). She had a primary duodenal tumor removed in 2009 using the Whipple procedure. At that time 4 liver metastases were noted. She saw Dr. Weber in 2010 because of two rapidly emerging liver metastases. A first photodynamic therapy (PDT) was done in May 2010. She felt much better. In June 2010 a second PDT course was given. An MRI scan of the liver in July 2010 no longer showed any metastases. However, in December 2010 metastases reappeared in her liver, which were treated with 3 more sessions of PDT in January of 2011. The metastases were still growing slowly. Dr. Weber decided to do a combination treatment with systemic PDT involving Chlorin E6, a photosensitizer and treating the metastases at the same time with interstitial laser therapy. Red light was used to stimulate the Chlorin E6. Miraculously the liver metastases became necrotic two weeks after this 20-minute treatment. Subsequently a surgical team from the University of Göttingen, Germany did a partial liver resection. At this point she appeared stable and cancer free.

Photodynamic therapy of a group of inoperable prostate cancer patients

20 patients with prostate cancer were treated with photodynamic therapy (PDT) between May and September 2014 (Ref.3). 20% of them had a complete remission of their cancers. 35% experienced a partial remission; another 35% had no further tumor progression. In 10% the tumors progressed. These patients were given the following photosensitizers: 80 mg Chlorin E6, 10 mg Hypericin and 150 mg Curcumin intravenously. Three hours after the intravenous photosensitizers had been given photodynamic laser therapy (PDT) was administered through a transparent, permanent catheter that allowed admission of the laser instrument up to the level of the prostate. With this approach the low-dose laser light penetrated the entire prostate gland. Three frequencies were employed that corresponded to the absorption peaks of the three photosensitizers, red light (658 nm) to activate Chlorin E6, yellow light (589 nm) to activate Hypericin and blue light (405 nm) to activate Curcumin.

In addition to PDT patients also received an immunostimulator preparation, called Gc protein-derived macrophage activating factor (GcMAF). Finally, in order to take advantage of the minimal differences regarding poor oxygenation of cancer cells versus good oxygenation of normal tissues intravenous oxygen was given with the oxygenation system of the German company Oxyven. This strengthened the normal tissue and weakened the cancer tissue.

The German researcher, Dr. von Ardenne did extensive research about the effects of oxygenation on healthy tissue versus cancer tissue. He postulated for instance that it would be possible to prevent cancer from metastasizing, if a person would exercise regularly while breathing oxygen through a mask. However, at this point this thought is not universally accepted.

When all the effects are taken together, the photodynamic therapy with photosensitizers and specific laser frequencies, the immune therapy and the oxygen therapy, the above successes in treatment outcomes can be explained as a synergistic effect: cancer cells are dying off from the PDT, macrophage activating factor stimulates the immune system and healing can start to occur.

Other end-stage cancer pilot studies

Dr. Weber reports about other pilot studies involving end stage breast cancer and pancreatic cancer (Ref.3).

Two cases of breast cancer with primary lesions measuring 3.5 cm or 5.0 cm were treated with Chlorin E6 and subsequent photodynamic laser therapy using the systemic and interstitial red laser of the Weber system. Within a few days tumor necrosis was visible and within 6 weeks after the PDT no tumor was present anymore in both cases.

Another case was an end stage pancreatic cancer in a 76-year-old man. This cancer was surgically removed in August of 2012. A few months later malignant ascites developed (cancer spread within the abdominal cavity). Chemotherapy with Gemzar had to be abandoned because of severe side effects. At this point PDT was started using Chlorin E6 twice with intraabdominal and intravenous red laser treatment. The patient also received a low-dose chemotherapy treatment with the pro-drug Xeloda, which gets converted into 5-fluoro-uracil (a standard chemotherapeutic agent). Using blue laser activation Xeloda becomes 100-times more powerful in destroying tumor cells. Only 3 months after this treatment the “incurable” pancreas cancer patient had been cured of his tumor and the malignant ascites. Initially the patient also had a secondary severe anemia that had to be treated with several blood transfusions before the PDT was started. Histology samples could no longer demonstrate presence of pancreatic tumor cells and the “intractable” anemia was cured as well.

Can Cancer Be Beaten?

Can Cancer Be Beaten?

Historic studies involving mega vitamin doses on end-stage cancer patients

Ref. 4 describes an experiment by Dr. Hoffer, the father of orthomolecular medicine. This is a branch of medicine that uses large doses of vitamins and minerals to rectify metabolic changes in various diseases. Dr. Hoffer treated 131 advanced cancer patients between 1976 and 1988 with a mixture of mega vitamins and minerals. There was a control group (not taking anything) and the experimental group. The results of this 9-year follow up study are depicted in the image below. The Y-axis represents the % of survival (at the zero point of time 100 % of each group were alive), the X-axis shows the time of survival in years. Note that the group of cancer patients taking meta vitamins is depicted with orange columns, the control group with blue columns. At 7 years of follow-up none of the controls survived. On average there was an 8 year survival advantage of the mega vitamin group versus the control group (control group 28% survival at year 1 of follow-up, mega vitamin group 34% survival at year 9 of follow-up). The supplements consumed were as follows:

Vitamin C, 10,000 to 40,000 mg orally daily; vitamin B3 (niacin or niacinamide) 300 to 3,000 mg; vitamin B6 (pyridoxine) 200 to 300 mg; folic acid 1 to 30 mg; vitamine E succinate 400 to 1,200 IU;  Coenzyme Q10 300 to 600 mg; selenium 200 to 1,000 micrograms daily; zinc 25 to 100 mg; calcium and magnesium supplement (2:1 ratio); mixed carotenoids as carrot juice; multivitamins and minerals.

Ref. 4 (page 347) explains that the Mayo Clinic did a study where they “duplicated” Dr. Hoffer’s study using only high doses of vitamin C, but failed to show any cancer fighting effect. However, they neglected to include all of the other cancer fighting supplements listed above. Vitamin C is an antioxidant, stimulates the immune system, but does not fight cancer by itself.

Dr. Hoffer's End Stage Cancer Experiment

Dr. Hoffer’s End Stage Cancer Experiment (click to enlarge)

Conclusion

Cancer treatments are entering a new phase where with the help of multiple treatment modalities combined (PDT, immunostimulation, oxygen therapy and low-dose laser activated chemotherapy) it is now possible to cure many cancers that were untreatable in the past. The tunnel vision approach of conventional oncology with a combination of surgery, chemotherapy and radiotherapy is obsolete for cases where cancer has metastasized. At this point the methods described in this blog are still considered experimental. In Germany they have done phase 1 and phase 2 trials as indicated above. Large phase 3 trials will have to be performed involving various types of cancers through conventional cancer agencies. Intravenous and interstitial photodynamic therapy is replacing the traditional toxic ways to treat cancer.  These new methods are effective with regard to both the primary tumor and metastases with hardly any side-effects.

Please note that Dr. Schilling has no commercial interest in Dr. Weber’s low-dose laser system, the links provided in this blog are merely there because of the newest information about low-dose laser photodynamic cancer therapy. Anybody who needs more information about the equipment or medical personnel wanting to buy the low-dose laser equipment can contact Jonathan Schwartz at this email: medicalmarvels@yahoo.com

References:

Ref.1: Þ. Lukðienë and P. De Witte: “Hypericin-based Photodynamic Therapy:I. Comparative Antitumor Activity and Uptake Studies in Ehrlich Ascite Tumor” Acta medica Lituanica. 2002. T. 9, Nr. 3, p. 195-199.

Ref.2: Michael Weber, MD: “New options of interstitial and intravenous laser therapy in oncology” The Intern.J. Med. Laser Applic. Vol1, July 2011, p.66

Ref. 3: Michael Weber, MD: ”Intravenous and interstitial photodynamic laser therapy: New options in oncology.” To be published 2015.

Ref. 4: Andrew W. Saul, PhD: “The Orthomolecular Treatment of Chronic disease”, Basic Health Publications Inc., Laguna Beach, CA 92651, 2014.