Some drugs have been discovered and they strengthened immunity in different ways, but they have not been considered as part of the treatment against cancer. Nevertheless, by including some of these drugs as part of a patient’s treatment plan, the chances of fighting cancer were significantly improved.
There are several drugs that have achieved amazing results when they have been incorporated into the treatment of patients, some of these drugs are aspirin, sitagliptin —a drug for the treatment of diabetes), and Cialis —a drug for erectile dysfunction. In addition, there are other drugs approved for uses different than cancer and that manage to enhance the immune response.
In its early days, 2,400 years ago, aspirin was used to treat fevers and pain. Its origins can be traced to the common white willow, whose bark and leaves have been used medicinally by Native Americans, ancient Egyptians, and ancient Greeks since the fifth century BC, when Hippocrates first wrote about it. The bark contains a chemical called salicin, which was chemically isolated in the early 19th century. Unfortunately, the pure chemical also caused serious stomach upsets, so it had a limited use. However, towards the end of the 19th century, while working for Bayer Laboratories, the German chemist Felix Hoffman created a synthetic form of the chemical that comes from aspirea, which also has a long history of use in traditional medicine, and it was easier on the stomach. The chemical, acetylsalicylic acid, proved effective in relieving pain, inflammation, and fever. It was by adding an “a” to the world “spiraea” and removing the Latin ending by replacing it with a simple “n” that the name aspirin was born. Aspirin is now one of the most widely used drugs in the world and it is used to treat not only headache, but also arthritis, heart attacks and also cancer.
Aspirin has not changed too much; it has just evolved. Aspirin is classified as a nonsteroidal anti-inflammatory drug (NSAID). NSAID is group of drugs that reduce pain and inflammation and have even been shown to help reduce colorectal cancer.
Along with aspirin, ibuprofen, and naproxen (brand name Aleve) are among the NSAIDs, which work by inhibiting the activity of the enzyme’s cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).
Studies have shown that combining immune checkpoint inhibitors with aspirin can reverse the tumor’s ability to evade the immune response.
It is hard to get an exact picture of how NSAID treatment would impact survival, but if you make a rough estimate based on information from the American Cancer Society that 40,000 American women will die of breast cancer, 6% could mean up to 2,500 lives that are saved each year only in the United States. Similarly, especially for breast cancer patients, it is important to understand the importance of ketorolac for a biopsy. There are no good studies on this subject, and in cases where the cancer has spread, sometimes surgery is to blame, this is due to increased growth factors being released.
Similar studies have not been done on the effectiveness of injecting aspirin directly into tumors, perhaps because while intravenous aspirin is fairly common in Europe, the FDA has not approved aspirin for intravenous use in the United States. However, a study has shown that intravenous aspirin is effective in treating migraines. In addition, the injection of aspirin is the most effective route, although if it is administered orally, it is recommended to take two doses of 325mg each morning and each night.
Despite its effectiveness, aspirin is not appropriate for all patients. Side effects can include nausea, vomiting, rashes, and kidney damage. Furthermore, aspirin can worsen asthma and cause internal bleeding in the stomach, intestines, and brain, as well as increase the risk of a perforated ulcer. Children and adolescents should not take aspirin, as there is a risk of developing Reye’s Syndrome, which affects the brain and liver. According to the aforementioned, it is recommended to take high doses of aspirin as part of a cancer treatment, only under the direction and supervision of a doctor. It is not recommended to self-medicate.
References:
Williams, J. (2019, 15th October) The Immunotherapy Revolution. Pg 102-106
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The post Immunotherapy for both advanced and early stage cancers appeared first on Williams Cancer Institute.
It is important to know that immunotherapy is a treatment that helps the immune system detect or recognize cancer cells in the body and destroy them.
It is known that melanoma or skin cancer is caused by high exposure to the sun’s rays or UV radiation such as tanning beds, or also to genetic changes in DNA.
Melanoma is the most aggressive and dangerous type of cancer that exists.
However, fortunately there is a method that helps people with this type of cancer, especially patients who present this disease in its most advanced form, that is, in phases 3 and 4, but at the same time it is still possible to achieve an effective treatment using immunotherapies even before any type of surgery to help remove the tumor itself.
It has been detected that immunotherapy in patients with melanoma can be enormously beneficial since the immune system attacks cancer cells not only in the initial tumor but also in other parts of the body where it has spread.
Studies have shown that immunotherapy is more effective if it is done before surgery than after it. In the same way, it has been discovered that adjuvant therapies have become a fundamental part of immunotherapy treatments, whose main objective is to destroy all malignant cells that could not be eliminated by surgery and even those that could not be detected.
It is important to know that it is very favorable, for the patient with some type of melanoma, to start immunotherapy before surgery since there would be a better response from T cells. Moreover, these cells would be capable of recognizing and attacking the tumor before and after the surgery.
References:
La inmunoterapia antes de la cirugía es eficaz contra el melanoma. (2022,
November 9th). Instituto Nacional del Cáncer. https://www.cancer.gov/espanol/noticias/temas-y-relatos-blog/2022/melanoma-inmunoterapia-antes-cirugia
The post BENEFITS OF IMPLEMENTING IMMUNOTHERAPY BEFORE SURGERY IN PEOPLE WITH MELANONA appeared first on Williams Cancer Institute.
Just like chemotherapy and ablation, radiation kills tumors. Then, residues of the dead tumor tissue can act as antigens sent to the immune system. In general, radiation therapy can be considered immunosuppressive, but when it is combined with the immunotherapy process it creates a synergy.
Overall, Cryoablation is considered to be more effective than radiation in its ability to stimulate an immune response. However, it will be easier for most patients to choose a radiation procedure than cryoablation.
It is much easier to get health insurance coverage for a radiation procedure. Therefore, most patients go to this process, where it is also advisable to receive immunotherapy treatment.
Although there is evidence of the effectiveness of the applicability of this combination, finding a doctor who is willing to perform it is a complex process to achieve. Without a doubt, cryoablation should be the first choice, however, it is important to know the radiation characteristics.
One of the main functions of radiation is to cause the immune system to identify malignant cells and destroy them. Radiation can also activate the stimulator of interferon gene pathways (STING), which can stimulate a nonspecific innate immune response. On the other hand, this process can cause the release of FCT-B and VEGF, both are immunosuppressive. In addition, radiation can lower the white blood cell count, a condition that is associated with immune suppression.
There are many studies testing the combination of radiation with immunotherapy. There are still some issues to define: What is the appropriate dose to be administered in radiation therapy? How often should it be administered? Once the radiation process has begun, at what point is it recommended to perform immunotherapy? before, after or during the process? There are conflicting studies regarding these treatment details.
In some cases, patients have not had results with immunotherapy, but later when the radiation process was added, the immune response was activated.
So, there are some real potential benefits, and certainly patients who have not had good results with immunotherapy might want to consider adding radiation processes to help activate the immune response.
Some benefits could be derived from previous traditional cancer treatments such as chemotherapy and radiation associated with an anti-cancer immune response. There are currently numerous studies being carried out. The only factor to consider when it comes to chemotherapy is that most studies focus on the traditional method of administering the maximum tolerated dose. However, science has shown that it is more effective to administer a lower dose, but more frequently. Some doctors offer a low dose, metronomic chemotherapy, however, many of them are not oncologists, so it is advisable to seek appropriate advice.
Also, for a patient with cancer with large tumors, chemotherapy and radiation may be helpful in reducing the tumor burden, so that the immune system can fight it off.
More remains to be learned about when therapy should be administered. For example, studies in mice have shown that cyclophosphamide given before chemotherapy, doxorubicin for example, can stimulate an immune response against cancer, but the reverse suppresses the immune response. These types of findings can be variable depending on the type of cancer and its location, as well as the local immune environment of the tumor, which can significantly affect immune responses.
Although it is still being evaluated, this topic has been discussed at immunology meetings and conferences. There, it is discussed that if the maximum dose chemotherapy is applied first, it can reduce the success potential of the immunotherapy that is carried out later. This is probably related to suppression of the immune response.
References:
Williams, J. (2019, 15th October) The Immunotherapy Revolution. Pg 72-75
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Black cumin seed oil is obtained from a small plant that comes from Southwest Asia, the Middle East, southern Europe, and North Africa. This plant produces tiny fruits from which oil is extracted and it has been used for more than 2,000 years due to its multiple benefits.
This plant is rich in antioxidants that are extremely important for health as they help protect cells against damage caused by unstable molecules called cell free radicals.
Moreover, antioxidants have been shown to help reduce inflammation and protect the body against illness such as heart disease, Alzheimer’s disease and cancer, as this oil is rich in thymoquinone, which has powerful antioxidant and anti-inflammatory effects.
Besides, this oil can protect brain health and help in the treatment of different types of cancer since it strengthens the immune system.
Black seeds and black cumin seed oil may reduce the side effects of chemotherapy treatments for different types of cancer, as they contain different active nutritional ingredients such as thymoquinone, which has been tested in patients and in laboratory studies. One of the main benefits of this seed is the reduction of fever and infections due to low neutrophil count in pediatric brain cancers, the reduction of toxicity side effect related to methotrexate (chemotherapy) in leukemia and a better response in patients with breast cancer treated with tamoxifen therapy.
Due to its high concentration of thymoquinone, omega 3 and carotenoids, cumin seeds could work as complementary foods that help us prevent cancer. These essential nutrients help protect cells against damage caused by oxidative stress and also help remove toxins. Therefore, they can also be useful to reduce the risk of suffering some cancers such as lung, kidney, prostate, liver, colon or skin.
When our body is attacked by cancer, it is important to start immunotherapy treatments and start adapting different lifestyles to improve our health. For example, regarding a new diet, it is advisable to supplement the diet with some natural products such as black cumin seed oil, which is an excellent helper in the fight against cancer because it is one of the natural supplements that has extensive preclinical data in cancer cell lines and animal models.
In the same way, it is advisable to consult with an immunotherapy specialist on issues related to the consumption of this product, since it is important to personalize nutrition for cancer treatments and specific treatment to obtain the benefits of nutrition.
References:
Cogle, C. R. (2022, 15th June). Aceite de semilla negra: aplicaciones en cánceres tratados con quimioterapia y efectos secundarios. addon.life. https://addon.life/es/2020/11/23/black-seed-chemo-side-effect/
McGrane, M. K. S. (2021, 27th September). Aceite de semilla negra: Beneficios, dosis y efectos secundarios. Healthline. https://www.healthline.com/health/es/aceite-de-semilla-negra
The post BLACK CUMIN SEED OIL POTENTIAL CO-ASSISTANT IN THE TREATMENT OF CANCER appeared first on Williams Cancer Institute.
Galvanize Therapeutics Presents Clinical Data Using Pulsed Electric Field (PEF) Energy for Non-Small Cell Lung Cancer
Galvanize Therapeutics aims to become the global leader in delivering medical technology innovations that drive biologic processes to treat a range of diseases, starting with treating chronic bronchitis symptoms, cardiac arrhythmias, and solid tumors. (PRNewsfoto/Galvanize Therapeutics)
NEWS PROVIDED BY
Galvanize Therapeutics, Inc.
Nov 10, 2022, 08:00 ET
INCITE ES clinical study results suggest the Aliya
PEF system may stimulate an immune response
BOSTON, Nov. 10, 2022 /PRNewswire/ — Galvanize Therapeutics, Inc., a commercial-stage biomedical platform company operating at the convergence of engineering, biology and healthcare delivery, today announced promising clinical data using its Aliya Pulsed Electric Field (PEF) system in patients with non-small cell lung cancer (NSCLC).
Initial results from the INCITE-ES clinical study conducted outside of the U.S., presented at this week’s Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting, indicate that the Aliya PEF system has the potential to stimulate an immune response in NSCLC patients.
INCITE-ES is a prospective, two-arm, non-randomized, concurrently controlled, multi-center treat-and-resect study in patients with suspected or confirmed NSCLC stage IA2-IB. In 30 patients PEF energy was delivered to a solitary tumor either percutaneously or endoscopically at the time of biopsy, prior to surgical resection. Eight additional patients were enrolled in the non-treated control group. Data presented previously demonstrated safety and feasibility to deliver PEF with no device or procedure-related adverse events. In an initial cohort of 10 PEF treated patients, tertiary lymphoid structures (TLS) [average 43.1 ± 41.0, (range 5-113)] were observed within tumors post-PEF, whereas none were identified on pre-PEF biopsy. TLS accumulation was greater in the PEF treated group as compared to the non-treated control group. TLS formation, shown in other studies to generate anti-tumor immunity¹, is emerging as a strong prognostic and predictive biomarker2 associated with patient survival benefits in NSCLC3,4.
“The five-year survival rate for NSCLC has only modestly improved from 13% in the 1970s to 21.7% in 20195, despite advances in surgery, radiation and advanced therapeutics,” explained Marcelo Jimenez, MD, PhD, Professor of Surgery, Thoracic Surgery Department, Salamanca University Hospital, Spain, investigator in the INCITE ES clinical study. “New treatment approaches are critically needed in NSCLC, and early indications of the potential for pulsed- electric field energy to activate the patient’s immune system are very encouraging. I look forward to future studies assessing this novel immuno-oncology approach in more patients.”
“These early clinical data build upon the recent U.S. Food and Drug Administration (FDA) 510(k) clearance for the Aliya system for soft tissue ablation and add to our confidence that PEF has the potential to mutually kill target cells and create immunogenic molecules,” said Jonathan Waldstreicher, M.D., Founder and CEO of Galvanize Therapeutics. “We are eager to expand our clinical program to further understand the opportunity for PEF to stimulate the immune system to activate against NSCLC and other solid tumors.”
About Aliya PEF System
The Aliya PEF system delivers non-thermal, high-voltage, high-frequency electrical currents through a single monopolar electrode placed in the target tissue. The PEF energy destabilizes the cells, resulting in cell death.
The non-thermal modality of the Aliya PEF system preserves surrounding healthy tissue, enabling ablation near critical structures, such as nerves and blood vessels. The Aliya waveform and electrode are designed to maximize the potential for releasing tumor antigens and may stimulate an immune response, potentially disrupting the immunosuppressive tumor microenvironment.
The Aliya System is 510(k) cleared in the United States for the surgical ablation of soft tissue. It is not currently commercially available in any other geography.
About Galvanize Therapeutics
Galvanize Therapeutics aims to become the global leader in delivering medical technology innovations that drive biologic processes to treat a range of diseases, starting with treating chronic bronchitis symptoms, cardiac arrhythmias, and solid tumors. Formed by ATP (Apple Tree Partners) in 2022, Galvanize is based in San Carlos, Calif., and is researching and commercializing its revolutionary Aliya Pulsed Electric Field (PEF) energy platform in the United States and Europe. For more information, please visit www.galvanizetx.com.
References:
1 Schumacher T N, Thommen D S. Tertiary lymphoid structures in cancer. Science. 2022; 375(6576):eabf9419.
2 Petitprez F, de Reynies A, Keung E. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020;577(7791):556 – 560.
3 Sautès-Fridman C, Petitprez F, Calderaro J. Tertiary lymphoid structures in the era of cancer immunotherapy. Nat Rev Cancer. 2019; 19:307 – 325.
4 Cottrell T R, Thompson E D, Forde P M. Pathologic features of response to neoadjuvant anti-PD-1 in resected non- small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann Oncol. 2018;29(8):1853-1860.
5 American Lung Association, State of Lung Cancer 2019
SOURCE Galvanize Therapeutics, Inc.
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It is known that chemotherapy is the treatment against cancer that better debilitate the immune system since the drugs used during chemotherapy affect divided cells rapidly. Likewise, this process is carried out by many of the body’s cells that can be found in the blood, the mouth, the digestive tract, the nose, the nails, the vagina, and the hair.
Cancer cells are damaged by chemotherapy because they cannot be repaired alone. Healthy cells can usually repair damage from chemotherapy after treatment is finished. One exception is nerve cells in the hands and feet, which some chemotherapy drugs can permanently damage. As chemotherapy drugs damage the bone marrow, the marrow is less able to make red blood cells, white blood cells, and platelets. The most significant impact typically falls on the white blood cells. If the body does not have enough white blood cells, the body is more vulnerable to infection.
In general, chemotherapy has been recognized to depress the immune system. It is common to see a decrease in white blood cells with chemotherapy. However, even in this reduction in white blood cell count, chemotherapy can stimulate the immune system.
This situation could be contradictory; however, it is known that the immune system can attack tumors and protect them. So, if you can debilitate protective cells, in other words, regulatory cells that include Tregs and CSDMs, you can achieve a positive balance in the immune response against cancer.
What are some of the beneficial effects that chemotherapy can have? One of these effects is the death of immunogenic tumor cells through mechanisms that cause tumor antigens to be released and danger signals to be stimulated. Tumors killed by these methods can help enhance an immune response.
Furthermore, increasingly cancer produces many immuno-inhibitory substances, both by direct protein production and by-products of its metabolism. If cancer growth is directly suppressed by chemotherapy, it can be reduced, facilitating the work of the immune system. Similarly, specific chemotherapy agents may be associated with increased immune response.
According to those mentioned above, if a person is going to have chemotherapy treatment and there is the option of using different drugs, it is more beneficial to use medicines that positively affect the immune response. In addition, it is essential to take advantage of the potential synergy with immunotherapy.
Without a doubt, it is a complicated process since most oncologists disagree with this combination of therapies; low-dose chemotherapy, also called metronomic dosing, seems more effective when it comes to stimulating an immune response. Unfortunately, this is not the way oncologists usually administer chemotherapy.
Although chemotherapy may be wished to be a memory of the past, it may still have a use, especially in the current situation of immunotherapy. If the patient has advanced cancer with extensive tumors, they might need help using chemotherapy treatment to give them a little more control so the immune system has a chance to fight it off. Otherwise, a rapidly growing advanced cancer may outpace the immune system. Cancer usually has a significant advantage at the beginning, and chemotherapy can slow it down, allowing the immune system to catch up.
It is essential to understand that metronomic chemotherapy is much more recommended since it is low-dose and can achieve many of the objectives of slowing down cancer and boosting the immune response against cancer.
References:
Cómo la quimioterapia afecta el sistema inmunitario. (s. f.). https://www.breastcancer.org/es/organizar-la-vida/sistema-inmunitario/tratamientos-contra-el-cancer/quimioterapia
Williams, J. (2019, 15th October) The Immunotherapy Revolution. Pg 72-75
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The first thing we must define is the ablation term itself. According to the NCI (National Cancer Institute), ablation in the field of medicine is the process or procedure by which the removal or destruction of a part of the body or tissue or its function is achieved. Ablation can be done through surgery, hormonal therapies, the use of medications, radiofrequency, heat, freezing, or other methods. 1
Percutaneous ablation encompasses a set of techniques that destroy pathological tissue using needles inserted through the skin. Sometimes liquid agents will be used (such as absolute alcohol) and in other physical agents, which can transfer heat (radiofrequency and microwave thermoablation) or cold (cryoablation) to the tumor.
The procedure will always be performed using image guidance, with computerized axial tomography to have constant control and safety during the introduction of the needle and that the energy transfer is applied exclusively to the tumor. This minimally invasive technique will be performed under sedation or general anesthesia, depending on certain parameters.
How is it performed? It consists of placing one or several needles in the center of the tumor to be treated very precisely and guided by an imaging technique. Using different technologies, these needles apply energy that destroys a volume of tissue in a predictable and controlled manner, thus eliminating the tumor. Ablation can be curative in some cases and has a high level of scientific evidence. Among the best-known ablation technologies are radiofrequency, microwaves, or lasers (they destroy tissue at high temperatures); cryoablation or cryotherapy (destroys tissue by freezing) and irreversible electroporation PEF (Pulsed Electric Field that destroys tissue without using heat or cold, instead using very short but very intense electrical pulses).
The most common way to perform an ablation is percutaneous, that is, with a needle from the skin without opening the patient. Compared to conventional surgery, ablation causes fewer complications and has a shorter recovery time. If the tumor is difficult to access percutaneously, ablation can also be performed in the operating room where, with the organ exposed and guided by ultrasound, the needle will be placed in the tumor. The organs that can be treated with ablation are liver tumors, lung tumors, kidney tumors, pancreatic tumors, bone and soft tissue tumors, and recently thyroid tumors. Ablation is a treatment that often can be combined with immunotherapy, chemotherapy, or radiotherapy.
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Cancer is an uncontrolled division of cells that have mutated and cause many problems in the body. In addition, these cancer cells have no control and spread throughout the body without any restriction, which is why they achieve to reproduce rapidly, causing metastasis.
Similarly, it is important to mention the metabolic endotoxemia, which causes several problems in the colon: the reproduction of cancer cells, for example. This is because cells known as intestinal bacteria dwell in the colon, which help in proper digestion in the body. There are cells that also help in the digestion of food that has not been digested by the body, this means that an unhealthy diet can cause the intestinal lining to leak, releasing metabolic endotoxins which act as inflammatory proteins that can lead to Colorectal cancer.
According to the aforementioned, studies supporting the fight against colorectal cancer have discovered a substance known as urolithin A, which is a product metabolite of pomegranate, which sustainably improves the function of immune cells in its fight against cancer.
Likewise, after research and treatment in colorectal cancer patients with urolithin A, more tumor-fighting immune cells have been detected, it has also been seen that this substance causes cytotoxic T cells to become stem cells with memory T that are supplied to the body with rejuvenated T cells and with energy.
Also, Treatment with urolithin A rejuvenates human T cells, also generates stem cells with memory T in the laboratory, all these findings have been found within the immune system, being the main defense against cancer.
Apart from this, pomegranate has been shown to have antiproliferative (prevents the reproduction of cancer cells) and pro-apoptosis (cell death caused by the same organism).
Unfortunately, people do not always react favorably to therapies due to the immune cells (T cells) are suppressed by the tissue surrounding the tumor, allowing the tumor to grow and spread, hence, this situation prevents these cells from accomplish their main function which is fighting cancerous tumors.
Urolithin A induces a biological that recycles and renews mitochondria, the cell’s “power plants” in T cells, through a process known as mitophagy. Aged and damaged mitochondria in T cells are removed and replaced with new, functional ones.
Additionally, Urolithin A limits tumor growth and even works simultaneously with existing immunotherapy. On the other hand, the benefits of urolithin A are also observed in human T cells since it produces a rejuvenation in them.
Without a doubt, foods rich in polyphenols such as pomegranate have the potential to reduce the levels of potentially harmful endotoxins in the blood that could help humans, especially those newly diagnosed with colorectal cancer and may help in the prevention or reduction of colorectal cancer.
Therefore, if you have been diagnosed with colorectal cancer, it would be very convenient to consume a greater amount of foods rich in polyphenols, such as pomegranates, blueberries, apples, vegetables, and red wine.
References:
Cogle, C. R. (2022, 15th July). ¿Puede el consumo de extracto de granada ayudar a reducir el riesgo de cáncer colorrectal? addon.life. https://addon.life/es/2021/07/31/c%C3%A1ncer-colorrectal-de-granada/
Staff, S. X. (2022, 20th October). Metabolite from pomegranates improves the function of immune cells in their fight against cancer. https://medicalxpress.com/news/2022-10-metabolite-pomegranates-function-immune-cells.html
The post THE UROLITIN A CONTAINED IN THE POMEGRANATE CAN HELP IN THE FIGHT AGAINST COLORECTAL CANCER appeared first on Williams Cancer Institute.
The best place where our system learns how to fight cancer is inside the tumor. There are new drugs in immunotherapy that can have powerful effects if they are used correctly. Numerous animals and few human studies have been conducted through injection of some of the FDA-approved immune checkpoint inhibitors, for example, anti-CTLA-4 and anti-PD-1, which show seem to be successful in systemic treatments with immune checkpoint inhibitors, such as Opdivo, Keytruda, and Yervoy. Likewise, the intratumoral injection of these drugs takes the patient much closer to a cure.
The OX40 receptor, also called CD134, is part of the superfamily tumor necrosis factor receptor, this is a co-stimulatory molecule and is expressed on activated and antigen-presenting T-cells. This receptor is the opposite of many of the other immunotherapy agents described above and which are widely used in current treatments, such as anti-PD-1 and anti-CTLA-4.
As described before, these agents block the receptors that are the brakes on the immune system. The OX40 would be equivalent to an “accelerator pedal”. The OX40 has a dual function; it can remove the brakes (regulatory cells) and increase the activation of T-cells (press the accelerator). Unlike traditional immune checkpoint inhibitor therapies used today, by using OX40 we are not blocking the receptor, we are activating it. As is common with most of these immune receptors, you can find them in many places, and they can work differently depending on where they are located. In this case, the OX40 agonist (stimulatory) antibody works in two ways, it stimulates immune activation, but it also binds to regulatory (inhibitory) cells and kills them. A simple way to describe it is that the OX40 agonist releases the brake and presses on the accelerator at the same time.
We are currently treating human patients with multiple types of cancer with the OX40/CpG agonist injected into the tumor. Thus, we have found that, in the case of humans, in order to achieve even better results, we have had to add the CTLA-4 inhibitor called Yervoy.
In immunotherapy, it is not only the correct combination of agents but also the correct sequence that is vital for success. Besides, there are some studies showing that immunotherapy applied in the wrong order, can adversely affect your future potential for a successful immune response. Hence, it is important to highlight that first it is necessary to stimulate the immune system to be attracted to the tumor.
For an effective immune response, the immune system not only needs to recognize cancer but drugs cannot be used systemically throughout the body by oral or intravenous administration. They must be used directly at the site of the tumor.
Furthermore, oncologists are not trained to inject into tumors, but they have the most control over the cancer treatment, and certain drugs injected into tumors will generate less profit than those administered systemically. There is an FDA-approved RTT agonist for topical use called Imiquimod, under the brand name Aldara. It is used for certain types of skin cancer and is being evaluated for topical use for breast cancer as well.
In addition, CpG´s are short single strands of DNA found in large numbers in certain bacteria. The immune system has evolved to recognize them as dangerous, which helps trigger an immune response. This is the main active component in Coley toxins, dead bacteria that Dr. Coley injected into tumors to help stimulate an immune response against cancer more than 100 years ago.
Moreover, the tumor environment does not have enough immune cells present when immune cells are present, we call it a “warm or swollen tumor environment,” which has a better prognosis. When immune cells are not present, we call it a “cold or desert tumor environment,” which has a poor prognosis. You need to have signals that attract immune cells to the tumor. However, this is a bit more complicated than you might think. Immune cells don’t swim toward a tumor. The cells that line the blood vessels must summon them. Since tumors control the local growth of blood vessels, to survive and avoid the immune response tumors build blood vessels that are less likely to attract immune cells, they have vessels that can attract regulatory cells to protect them and destroy effector T-cells (attackers) that want to kill them. Essentially, the tumor controls the pathways in this territory, so it will keep the enemy out. This is another barrier to the immune system.
In addition, CpGs have been shown to help initiate changes in blood vessels, which can then attract the required immune cells.
Finally, there are numerous techniques to stimulate an immune response in a tumor. It has been seen that in some cases the vaccines intended to prevent another disease, could inadvertently stimulate an immune response in cancer.
References:
Williams, J. (2019, 15th October) The Immunotherapy Revolution. (pp. 56-65)
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