In Vitro Evidence Of Human Immune Responsiveness Shows The Improved Potential Of A Recombinant Bcg Strain For Bladder Cancer Treatment
- 1Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil
- 2Programa de Pós-Graduação Interunidades em Biotecnologia USP-I.Butantan-IPT, São Paulo, Brazil
- 3Laboratório de Imunologia Aplicada, Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Carlos, Brazil
- 4Institute of Genetic and Biomedical Research, National Research Council, Cagliari, Italy
- 5Institute of Protein Biochemistry, National Research Council, Naples, Italy
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What Happens During Bcg Cancer Treatment
Before beginning BCG treatment, local anesthesia is given to numb the area and keep you comfortable. Next, your healthcare provider will place a catheter into your urethra and inject the liquid BCG solution into your bladder.
The BCG solution needs to come in contact with cancer cells to kill them. So, once the medication is injected, your healthcare provider will remove the catheter and ask you to lie on your back, stomach and both sides for 15 minutes each.
When the process is complete, youre free to leave your appointment. However, you should avoid peeing for at least one more hour.
How long do you hold BCG in your bladder?
Once the BCG solution is injected into your bladder, youll hold it for a total of two hours. After this point, youll be able to pee.
What does BCG do to the bladder?
When the BCG solution enters your bladder, your immune system cells begin to attack the cancer cells in your bladder.
BCG treatment schedule
The initial BCG cancer treatment occurs weekly for six weeks. This is called induction therapy.
If the treatment is working, your doctor may prescribe BCG maintenance therapy. Maintenance therapy is given once a week for three weeks at the three-, six- and 12-month marks. For some people, this may be continued up to three years.
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Whats Old Is New Again
Bacterial therapies for cancer are not new. They go back more than a hundred years to William Coley, whose eponymously named toxins were some of the first cancer immunotherapies ever developed. Dr. Coley was a surgeon at Memorial Hospital who noticed that people with cancer who got severe infections sometimes saw their cancers regress. He began administering a vaccine of heat-killed bacteria to patients in the hopes of spurring their immune systems to attack cancer. Dr. Coley had some success with his approach, but the results proved unpredictable and hard to replicate, so his toxins eventually faded from use.
Inspired by Dr. Coleys work, scientists at MSK continued to research immune-based treatments for cancer. This sustained research effort eventually led to the development of modern forms of immunotherapy, including immune checkpoint inhibitors. These drugs take the brakes off T cells and allow them to find and fight cancer cells that display unique neoantigens .
We show that BCG is similar to checkpoint inhibitors in that it works by eliciting an immune response against cancer neoantigens, says Gil Redelman-Sidi, a physician-scientist who collaborates with Dr. Glickman and is the co-corresponding author on the PNAS paper. These results bring BCG into the modern world of immunology.
Treating Complications Of Bcg Therapy
If you do experience a problem from BCG infection, you may need to receive targeted antibiotics, such as isoniazid and rifampin.
Complications of BCG therapy sometimes dont occur until years later. That can happen if the BCG bacteria that spread in the body become reactivated. These complications can sometimes be tricky to diagnose. Medical imaging might first make your clinician concerned about cancer or about another type of bacterial infection.
Make sure that all your medical care providers know that you have had BCG therapy. That will help guide their diagnostic process and ensure you get the best possible care. In some cases, your clinician will want a tissue sample from the involved area to make sure that the problem is from a BCG infection and not from some other source.
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Current Alternatives To Bcg
Research on improving NMIBC therapy has mainly focused on rescue patients who do not respond to BCG therapy, since BCG is truly efficacious in the majority of patients for avoiding recurrence and progression episodes. The alternative treatment options include virus and other bacteria different from BCG as vehicles for specific tumor growth inhibition agents or immunostimulatory components, chemotherapeutic agents, new delivery options for current therapies, and systemic immunotherapies that have to be demonstrated to be efficacious in other types of cancers .
Current alternative research for nonmuscle invasive bladder cancer treatment.
Virus-Based Treatments
Bacteria-Based Treatments
Chemotherapeutic Treatments and Improved Delivery
Different strategies can improve the use of chemotherapy for treating NMIBC. The appearance of new agents, the combination of different chemotherapeutic agents, the use of hyperthermia for improving intravesical instillation, or other strategies have been considered for improving the treatment of intermediate- and high-risk NMIBC patients.
The efficacy of intravesical therapies can also be improved through delivery adaptations such as hyperthermia, electromotive drug administration or new devices.
Checkpoint Inhibitors in Nonmuscle-Invasive BC
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Trained Immunity And Bladder Cancer
Trained immunity might also have a role in the effect of intravesical BCG for NMIBC as an anti-tumour mechanism. This role is not well defined data on epigenetic modifications in innate immune cells during intravesical BCG instillations are lacking. However, increased cytokine,, and chemokine, production by innate immune cells during intravesical BCG therapy is well described and might indirectly support a role for trained immunity in the mechanisms of BCG immunotherapy for NMIBC.
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Bcg: The Current Treatment Ofchoice For Bladder Cancer
Pharmacy Times
Mr. Sherman is president of ShermanConsulting Services Inc.
After arecent physical examination,my wife learned that redand white blood cells weredetected in her urine. The doctorordered an intravenous pyelogram todetermine the cause. In this test, aniodine-containing contrast material isinjected into the bloodstream, and aseries of x-rays is then taken at timedintervals. The resulting films allow theradiologist to view the entire urinarytract. Unfortunately, the diagnosis revealedthat my wife had bladder cancer,a well-differentiated papillary tumor,which fortunately could be completelyremoved by transurethral resection andfulguration.
The urologist told us that a high-gradetransitional type of tumor would requirethe instillation of chemotherapeuticdrugs such as mitomycin C or doxorubicin.Another option would be to useBacille Calmette-Gu?rin vaccineinstillations?-a treatment that controlssuperficial bladder cancer, particularlycarcinoma in situ. I was surprised tolearn that an ancient vaccine, originallydesigned to prevent tuberculosis , isemployed for a completely unrelatedindication and is the current treatment ofchoice for bladder cancer. I thought thatother pharmacists might be as curious asI was to learn more about the drug, itsdiscovery, and its alternative use.History?Tuberculosis
At best, the vaccineis 80% effective in preventingTB for a durationof 15 years. Onethird of clinical trialshave shown no protectiveeffect, however.5
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Cancer May Spread From Where It Began To Other Parts Of The Body
When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began and travel through the lymph system or blood.
- Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor in another part of the body.
- Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor in another part of the body.
The metastatic tumor is the same type of cancer as the primary tumor. For example, if bladder cancer spreads to the bone, the cancer cells in the bone are actually bladder cancer cells. The disease is metastatic bladder cancer, not bone cancer.
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Optimization Of The Use Of The Scarce Vials Of Bcg
As soon as BCG shortages began, different strategies were adopted at different levels, from improvements in BCG production to modifications of the recommended treatment.
Improving BCG Production
The production of BCG is not an easy matter. Due to the slow growth of the mycobacteria, any inaccuracy during the manufacturing process can lead to a large loss of time and money, as the BCG shortages have proven. For this reason, some researchers proposed optimizing BCG bulk production by modifying the growth in pellicles to the use of bioreactors or evaluating the possibility of extending the shelf life of the already manufactured BCG vials.
Regulatory Issues/Favorable Policies
Variations in Clinical Guidelines Recommendations
For intermediate-risk NMIBC patients
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Intravesical chemotherapy must be used as a first-option treatment instead of BCG. Induction once a week for six to eight weeks plus a monthly maintenance schedule for one year.
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For second-line treatment, a one-third dose of BCG instead of full-dose BCG can be used. In that case, different patients can be treated the same day clustered in groups of three to avoid BCG wastage.
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Maintenance BCG can be omitted.
For high-risk NMIBC
Who Can Have This Treatment
BCG is appropriate for noninvasive and minimally invasive bladder cancers. It usually follows a procedure called transurethral resection of bladder tumor . Its intended to help prevent recurrence.
This treatment only affects cells inside the bladder. Its not useful for later stage bladder cancer that has spread into or beyond the bladder lining, or to other tissues and organs.
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What Is Bcg Treatment For Non
BCG is an intravesical immunotherapy using a bacteria of Mycobacterium bovis that has been reduced to cause less harm to the body. The bacteria is still kept viable so that it can actively work in the body to kill the cancer cells.
Intravesical is a way in which a medication is put into the bladder. Liquid drugs are put directly into the bladder through a catheter.
BCG is used as a therapy for and protection against bladder cancers that come back after a period of time in patients that have a more aggressive bladder cancer diagnosis. It is currently the most effective treatment.
Origin Of Bcg And Its Relationship With Bladder Cancer
Mycobacterium bovis Bacillus Calmette-Guérin is a species originated after 230 recultures of the pathogen M. bovis. Over a period of thirteen years, Albert Calmette and Camille Guérin recultured isolated colonies from the originally pathogenic M. bovis. In 1921, they demonstrated that the obtained bacillus was not only non-pathogenic in animal models but also protected against tuberculosis challenge in vaccinated animals. Afterwards, the massive production of BCG was initiated for use in tuberculosis prevention in humans, and it is still the only commercially available vaccine against tuberculosis. At that time, the use of a mixture of two bacteria, Serratia marcescens and Streptococcus pyogenes, was investigated for cancer treatment, and the possibility to use the newly developed and safe BCG offered a novel therapeutic option for some cancer patients. Although some studies demonstrated the potential efficacy of the new BCG as a treatment for diverse types of cancer, it was not until the 1970s that BCG was approved as an immunotherapeutic treatment for bladder cancer patients.
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How Does Bcg Work Against Cancer
BCG stimulates the immune system to attack the bacteria found in the vaccine. In treating bladder cancer, BCG is injected through a catheter directly into the tumor. When the vaccine reaches cancer cells, it sends a wave of immune cells to attack the cancer. Some patients experience flu-like symptoms, including aches, fever and chills, for a couple of days after treatment.
BCG is a known immune stimulant that both generates an immune response related to a future exposure to the microbe responsible for tuberculous and also enhances the response an individual may develop when exposed later in life to other micro-organisms, says Maurie Markman, MD, President of Medicine & Science at Cancer Treatment Centers of America® .
As with any new treatment or vaccine, it may take months, even years, before doctors know whether BCG is a safe and effective weapon against the disease. Dr. Markman recommends pumping the breaks on expectations BCG or any other drug will be developed in short order. The hope is that existing pharmaceutical agents with possible clinically relevant activity against the virus may provide some level of meaningful benefit for individuals with mild or more serious symptoms, Dr. Markman says.
If you are a cancer survivor or in active treatment and are concerned about how the COVID-19 situation may impact you or your care, please contact your care team.
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After Bladder Cancer Has Been Diagnosed Tests Are Done To Find Out If Cancer Cells Have Spread Within The Bladder Or To Other Parts Of The Body
The process used to find out if cancer has spread within thebladder lining and muscle or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:
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Intravesical Therapy For Bladder Cancer
With intravesical therapy, the doctor puts a liquid drug right into your bladder rather than giving it by mouth or injecting it into your blood. The drug is put in through a soft catheter that’s put into your bladder through your urethra. The drug stays in your bladder for up to 2 hours. This way, the drug can affect the cells lining the inside of your bladder without having major effects on other parts of your body.
When Is Bcg Treatment Used
You may have BCG directly into your bladder after surgery to remove non-muscle-invasive bladder cancer. This type of surgery is called a transurethral resection of a bladder tumour .
This treatment helps prevent the cancer from coming back in the bladder lining. It also reduces the risk of the cancer becoming muscle-invasive. Doctors usually suggest this treatment if you have a high-risk bladder cancer, or sometimes if you have an intermediate-risk bladder cancer.
There is usually at least 2 weeks between the surgery to remove the cancer and the start of BCG treatment. This is to give your bladder enough time to heal from the surgery.
You usually have BCG treatment once a week for 6 weeks. This is sometimes called the induction course. You may be offered more BCG treatments. This is usually called maintenance treatment.
Treatment times vary. Your doctor will explain what is best for you.
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When To See A Doctor
There are a few side effects that can be especially dangerous, so make sure to talk to your doctor if you notice that you:
- Have a severe skin rash
- Are wheezing or having difficulty breathing
- Are finding swallowing to be difficult
- Have a high fever that isnt lowered with Tylenol or other over-the-counter fever reducers
Researchers Eye Cancer Drug Bcg As Potential Covid
The frantic search for ways to stop, prevent and treat COVID-19 has put the spotlight on a decades-old drug originally developed for tuberculosis , but currently used to treat bladder cancer. The Bacillus Calmette-Guerin vaccine, one of the most widely administered vaccines in the world to prevent TB, is now being researched as a potential COVID-19 vaccine. While the research into BCG has generated headlines worldwide, it may take some time to determine whether the drug is safe and effective against the virus, an often-painstaking process for any potential treatment.
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Treatment Of Recurrent Bladder Cancer
For information about the treatments listed below, see the Treatment Option Overview section.
Treatment of recurrentbladder cancer depends on previous treatmentand where the cancer has recurred. Treatment for recurrent bladder cancer mayinclude the following:
- Radiation therapy as palliative therapy to relieve symptoms and improve quality of life.
- A clinical trial of a new treatment.
Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.
What Happens During Treatment
A urinary catheter is inserted through your urethra and into your bladder. Then the BCG solution is injected into the catheter. The catheter is clamped off so the solution stays in your bladder. Some doctors may remove the catheter at this time.
You have to hold the medicine in your bladder. Youll be instructed to lie on your back and to roll from side to side to make sure the solution reaches your entire bladder.
After about two hours, the catheter is unclamped so the fluid can be drained. If the catheter was already removed, youll be asked to empty your bladder at this time.
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