Monoclonal Antibodies For Prostate Cancer

Notes When Using Monoclonal Antibodies To Treat Cancer

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Current Treatments For Prostate Cancer

Many patients with prostate cancer do not require treatment as it is a slow-growing type of cancer, and active surveillance is often adequate. Others are successfully treated. However, others will experience the cancer spreading to other organs . Metastatic prostate cancer can be controlled with hormone therapy, but eventually this type of therapy may stop working. Anywhere from 10-50% of metastatic prostate cancers will evolve into a state known as metastatic castration-resistant prostate cancer within 3 years. Despite recent advances in treatments for mCRPC, this disease is considered incurable and has a prognosis of only 2-3 years.

The cancer therapies generally considered for prostate cancer include radical prostatectomy, radiation therapy, chemotherapy, brachytherapy, and hormone therapy. Another type of therapy that has been used successfully in many types of cancer is monoclonal antibody therapy. Thus far, using monoclonal antibodies in treating prostate cancer has not been very successful. A type of MAb called checkpoint inhibitors has demonstrated deep and durable responses for a range of cancers but limited success in prostate cancer. This may be because prostate cancers are difficult for the immune system to see and are hard to access due to chemical and physical barriers around prostate tumors. However, a recent study has shown some promise in using MAb therapy for mCRPC patients.

Apalutamide With Or Without Stereotactic Body Radiation Therapy In Treating Participants With Castration

open to eligible males ages 18 years and up

This phase II trial studies the how well apalutamide with or without stereotactic body radiation therapy work in treating participants with castration-resistant prostate cancer. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. It is not yet known whether giving apalutamide with or without stereotactic body radiation therapy works better in treating participants with castration-resistant cancer.

San Francisco, California

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For46 In Combination With Enzalutamide In Patients With Metastatic Castration Resistant Prostate Cancer

Sorry, not yet accepting patients

This is a Phase 1b/2 study evaluating FOR46 in combination with enzalutamide in patients with metastatic castration resistant prostate cancer after prior progression on abiraterone. FOR46 is designed to target and bind to CD46, a transmembrane cellular protein expressed at moderate or high levels in numerous cancer types. The investigators hypothesize that the combination of FOR46 plus enzalutamide will achieve a clinically significant composite response rate with sufficient durability of response in mCRPC patients.

San Francisco, California

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Monoclonal Antibodies For Targeted Cancer Therapy

How do monoclonal antibodies fight cancer?

Monoclonal antibodies are laboratory-created immune system proteins. Antibodies are naturally formed by the body and assist the immune system in recognizing and marking microorganisms that cause disease, such as bacteria and viruses, for elimination. Monoclonal antibodies, like your bodys own antibodies, identify particular targets.

Numerous monoclonal antibodies are utilized in cancer treatment. They are a form of targeted cancer therapy, meaning they are specifically engineered to interact with certain cancer cells.

Certain monoclonal antibodies are also used in immunotherapy, as they assist the immune system in turning against cancer.

For instance, some monoclonal antibodies label cancer cells to aid the immune system in recognizing and eliminating them. Rituximab, for example, attaches to a protein called CD20 on B cells and some kinds of cancer cells, signaling the immune system to destroy them. B lymphocytes are a subset of white blood cells.

Types of cancer treated by Monoclonal antibodies

Monoclonal antibody treatments have been developed for a variety of cancers, though not all. Certain types of cancer cells are more responsive to monoclonal antibody treatments than some others.

What are the complications associated with monoclonal antibodies?

The following are examples of needle site reactions:

• Inflammatory lung disease
• Sores in the mouth and skin that can develop into serious infections

• Difficulty breathing

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Monoclonal Antibodies In Ovarian And Prostate Cancer

Radioimmunoscintigraphy using radiolabeled monoclonal antibodies to image diseaseis a growing subspecialty of nuclear medicine. RIS of the reproductive tracts of men and women has shown encouraging results in imaging both primary lesions and metastases of these cancers. Ovarian cancer is the most fatal gynecologic cancer in the United States, and prostate cancer is the most prevalent form of cancer in men. Several MoAbs against reproductive tumor antigens were used with limited success in clinical trials before 1989. Most recently, MoAbs CYT-103 and OV-TL 3 have shown promise as safe, sensitive imaging tools for ovarian cancer. Although to date more agents have been used to image ovarian carcinoma than prostate cancer, research has been restimulated in prostate carcinoma imaging because of development of a promising MoAb conjugate, CYT-356. Radionuclide indium-111 appears to be the most promising radiolabel to date for ovarian and prostate carcinoma RIS performed in the United States. In future clinical trials, consideration of safety issues and a standardization of methods among institutions using RIS are needed before the use of MoAb technology in cancer imaging will become routine. Comparative studies with more traditional methods like computed tomography are needed, as well as more trials comparing radioimmunoscintigraphic findings with pathological evidence.

How Do Monoclonal Antibodies Work Against Cancer

Monoclonal antibodies are immune system proteins that are created in the lab. Antibodies are produced naturally by your body and help the immune system recognize germs that cause disease, such as bacteria and viruses, and mark them for destruction. Like your bodys own antibodies, monoclonal antibodies recognize specific targets.

Many monoclonal antibodies are used to treat cancer. They are a type of targeted cancer therapy, which means they are designed to interact with specific targets. Learn more about targeted therapy.

Some monoclonal antibodies are also immunotherapy because they help turn the immune system against cancer. For example, some monoclonal antibodies mark cancer cells so that the immune system will better recognize and destroy them. An example is rituximab, which binds to a protein called CD20 on B cells and some types of cancer cells, causing the immune system to kill them. B cells are a type of white blood cell.

Other monoclonal antibodies bring T cells close to cancer cells, helping the immune cells kill the cancer cells. An example is blinatumomab , which binds to both CD19, a protein found on the surface of leukemia cells, and CD3, a protein on the surface of T cells. This process helps the T cells get close enough to the leukemia cells to respond to and kill them.

Some monoclonal antibodies bring t cells close to cancer cells, helping them kill cancer cells.

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Platform Study For Prostate Researching Translational Endpoints Correlated To Response To Inform Use Of Novel Combinations

open to eligible males ages 18 years and up

This study is designed to evaluate multiple clinical hypotheses and mechanistically-defined combinations to evaluate the safety and efficacy of immunotherapy combinations in participants with mCRPC who have received prior secondary androgen receptor signaling inhibitor therapy .

San Francisco, California

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Newer Treatments For Early

Researchers are looking at newer forms of treatment for early-stage prostate cancer. These new treatments could be used either as the first type of treatment or after unsuccessful radiation therapy.

One treatment, known as high-intensity focused ultrasound , destroys cancer cells by heating them with highly focused ultrasonic beams. This treatment has been used in some countries for a while, and is now available in the United States. Its safety and effectiveness are now being studied, although most doctors in the US dont consider it to be a proven first-line treatment for prostate cancer at this time.

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Intratibial Injection Of Pc3 In Scid Mice

Eight-week-old male SCID mice were anesthetized using an injection of pentobarbital and then of buprenorphine for surgical analgesia. Each was given a medial parapatellar incision and a needle was placed in the intramedullary canal of the tibia. PC3 cells, at a concentration of 2×105/100 l, were slowly injected into the tibia and the incision was closed with 50 chromic sutures. For postoperative analgesia, buprenorphine was injected once daily for 3 days post-surgery. The success rate for intratibial tumor implantation was 100%. The mice were then randomly assigned to three groups and injected with vehicle , mIgG , or 7E three times per week. Seven weeks after treatments began, the mice were killed using CO2, and their tibial metaphyses were analyzed in vivo using micro-computed tomography with a high-resolution, low-dose X-ray scanner. Bone mineral density was analyzed in 50 consecutive slices. The results were calculated as a percentage versus values from a healthy control.

Treatment With Nivolumab And Ipilimumab Or Nivolumab Alone According To The Percentage Of Tumoral Cd8 Cells In Advanced Metastatic Cancer

open to eligible people ages 18 years and up

This is an open-label, exploratory study to evaluate nivolumab with or without ipilimumab based on percentage of tumoral CD8 cells at the time of treatment in participants with varying advanced solid tumors. Participants who have a tumor with ⥠15% CD8 cells will receive nivolumab monotherapy, and participants who have a tumor with < 15% CD8 cells will receive ipilimumab in combination with nivolumab.

San Francisco, California

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What Are The Limitations Of Targeted Cancer Therapies

Targeted therapies do have some limitations. One is that cancer cells can become resistant to them. Resistance can occur in two ways: the target itself changes through mutation so that the targeted therapy no longer interacts well with it, and/or the tumor finds a new pathway to achieve tumor growth that does not depend on the target.

For this reason, targeted therapies may work best in combination. For example, a recent study found that using two therapies that target different parts of the cell signaling pathway that is altered in melanoma by the BRAF V600E mutation slowed the development of resistance and disease progression to a greater extent than using just one targeted therapy .

Another approach is to use a targeted therapy in combination with one or more traditional chemotherapy drugs. For example, the targeted therapy trastuzumab has been used in combination with docetaxel, a traditional chemotherapy drug, to treat women with metastatic breast cancer that overexpresses the protein HER2/neu.

How Are Targets For Targeted Cancer Therapies Identified

The development of targeted therapies requires the identification of good targetsthat is, targets that play a key role in cancer cell growth and survival.

One approach to identify potential targets is to compare the amounts of individual proteins in cancer cells with those in normal cells. Proteins that are present in cancer cells but not normal cells or that are more abundant in cancer cells would be potential targets, especially if they are known to be involved in cell growth or survival. An example of such a differentially expressed target is the human epidermal growth factor receptor 2protein . HER-2 is expressed at high levels on the surface of some cancer cells. Several targeted therapies are directed against HER-2, including trastuzumab , which is approved to treat certain breast and stomach cancers that overexpress HER-2.

Another approach to identify potential targets is to determine whether cancer cells produce mutant proteins that drive cancer progression. For example, the cell growth signaling protein BRAF is present in an altered form in many melanomas. Vemurafenib targets this mutant form of the BRAF protein and is approved to treat patients with inoperable or metastatic melanoma that contains this altered BRAF protein.

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How Are Targeted Therapies Developed

Once a candidate target has been identified, the next step is to develop a therapy that affects the target in a way that interferes with its ability to promote cancer cell growth or survival. For example, a targeted therapy could reduce the activity of the target or prevent it from binding to a receptor that it normally activates, among other possible mechanisms.

Most targeted therapies are either small molecules or monoclonal antibodies. Small-molecule compounds are typically developed for targets that are located inside the cell because such agents are able to enter cells relatively easily. Monoclonal antibodies are relatively large and generally cannot enter cells, so they are used only for targets that are outside cells or on the cell surface.

Candidate small molecules are usually identified in what are known as high-throughput screens, in which the effects of thousands of test compounds on a specific target protein are examined. Compounds that affect the target are then chemically modified to produce numerous closely related versions of the lead compound. These related compounds are then tested to determine which are most effective and have the fewest effects on nontarget molecules.

Monoclonal antibodies are developed by injecting animals with purified target proteins, causing the animals to make many different types of antibodies against the target. These antibodies are then tested to find the ones that bind best to the target without binding to nontarget proteins.

What Are The Side Effects Of Targeted Cancer Therapies

Scientists had expected that targeted cancer therapies would be less toxic than traditional chemotherapy drugs because cancer cells are more dependent on the targets than are normal cells. However, targeted cancer therapies can have substantial side effects.

The most common side effects seen with targeted therapies are diarrhea and liver problems, such as hepatitis and elevated liver enzymes. Other side effects seen with targeted therapies include:

• Problems with blood clotting and wound healing
• High blood pressure
• Gastrointestinal perforation

Certain side effects of some targeted therapies have been linked to better patient outcomes. For example, patients who develop acneiform rash while being treated with the signal transduction inhibitorserlotinib or gefitinib , both of which target the epidermal growth factor receptor, have tended to respond better to these drugs than patients who do not develop the rash . Similarly, patients who develop high blood pressure while being treated with the angiogenesis inhibitorbevacizumab generally have had better outcomes .

The few targeted therapies that are approved for use in children can have different side effects in children than in adults, including immunosuppression and impaired sperm production .

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Study Of Azd5305 As Monotherapy And In Combination With Anti

Sorry, not currently recruiting here

This research is designed to determine if experimental treatment with PARP inhibitor, AZD5305, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced solid tumors.

San Francisco, California and other locations

Combination Of Bipolar Androgen Therapy And Nivolumab

Sorry, in progress, not accepting new patients

Single arm, multicenter, open-label Phase II study of the effects of parenteral testosterone in combination with nivolumab in men with metastatic castration-resistant prostate cancer who previously progressed on at least one novel androgen-receptor targeted therapy . Up to one taxane agent is permitted.

San Francisco, California

Sorry, in progress, not accepting new patients

The purpose of this study is to assess the safety and activity of ARN-509 in men with advanced castration resistant prostate cancer. Patients will first be enrolled into Phase 1 of the study to identify a tolerable dose for the Phase 2 portion of the study. In the Phase 2, 3 different cohorts of patients will be enrolled to evaluate the safety and activity of ARN-509.

San Francisco, California

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What Lies Ahead: Leading The Way With Alpha Therapies

The coming years will see even more powerful forms of radioactive therapy. The MSK laboratory of radiochemist Jason Lewis and other researchers are investigating the use of alpha particles, which have a much higher energy hundreds of times more potent than the photons used in conventional radiation or beta particles. Not only do alpha particles cause more damage when they slam into cancer cells but their path of destruction is more tightly focused, sparing normal cells.

MSK is building one of the nations first dedicated alpha particle GMP labs at a U.S. academic institution.

These radiopharmaceuticals that we are creating translate very well from bench to bedside, says Dr. Lewis, Chief of the Radiochemistry and Imaging Sciences Service and Director of the Radiochemistry and Molecular Imaging Probe Core Facility. When you see these striking responses to treatment, it brings real hope for the future and our patients.

Advances in radiotheranostics are supported by The Tow Foundation, long-time contributors to MSKs mission.

• A new FDA-approved drug could be an effective treatment against prostate cancer that has spread.
• The treatment uses a molecule that seeks out and attaches to a specific protein on the cancer cell surface called PSMA
• The technology delivers radiation that damages DNA and destroys the cancer cell..