Prostate Cancer Immunotherapy

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  • Prostate Cancer
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

How is Immunotherapy for Prostate Cancer Changing the Outlook for Patients?

Reviewed By: Sumit K. Subudhi, M.D., Ph.D.
The University of Texas MD Anderson Cancer Center

Immunotherapy for prostate cancer includes two FDA-approved treatment options and is a promising area of research for metastatic cancer treatment.

The prostate is a small, walnut-shaped gland that is part of the male reproductive system. The prostate is located just below the bladder, where it surrounds the top portion of the urethra (the tube that drains urine from the bladder). The main function of the prostate gland is to secrete fluid that nourishes and protects sperm.

As the second most common male cancer in the world, prostate cancer affects roughly 1.3 million people and kills more than 360,000 people each year, which represents about 4% of all cancer deaths worldwide. In the United States alone, there will be roughly 192,000 new cases and more than 33,000 deaths in 2020. Prostate cancer, the eighth leading cause of cancer-related deaths, will impact an estimated 1 in every 7 men in their lifetimes.

In its early stages, prostate cancer is highly treatable, with five-year survival rates close to 100%. Once prostate cancer has metastasized, however, the 5-year survival rate  falls to less than 30%, highlighting a significant need for more effective treatment of advanced stage disease.

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Prostate Cancer Treatment Options

Conventional treatments for early-stage prostate cancer include surgery and radiation. Hormonal therapy, which can reduce levels of the male hormones (androgens like testosterone) that lead to tumor growth, is also used to treat early-stage tumors. For advanced or metastatic prostate cancer, chemotherapy is also a treatment option.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently two FDA-approved immunotherapy options for prostate cancer.

Cancer Vaccines

  • Sipuleucel-T (Provenge®): a vaccine composed of patients’ own immune cells, which have been stimulated to target the PAP (prostatic acid phosphatase) protein highly expressed on prostate cancers; approved for subsets of patients with advanced prostate cancer


  • Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced prostate cancer that has high microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H)

In cases where the patient's prostate cancer is resistant to testosterone level reduction via hormone therapy, treatment options are few. Several immunotherapy options are currently in clinical trials for patients with advanced prostate cancer.

Find a prostate cancer clinical trial

CRI's Impact in Prostate Cancer

Since 1953, the Cancer Research Institute has provided almost 100 grants to research and clinical trial initiatives in the field of prostate cancer, totaling almost $25 million in financial support.

In fact, $9 million of this funding was given in conjunction with the CRI Prostate Cancer Initiative—a program started in 1996 to support clinical research promising the most readily available and immediate benefits to prostate cancer patients. The CRI Prostate Cancer Initiative also aimed to improve prostate cancer patient outreach and increase public awareness of the disease.

Our organization has also participated in cooperative efforts to develop informative resources and materials for prostate cancer patients in close partnership with national nonprofit ZERO's patient support program.

Some work and recent findings by CRI investigators that are advancing the understanding and treatment of prostate cancer include:

  • In 2011, CRI researchers Alex Knuth, M.D., and Maries van den Broek, Ph.D., reported that the CT10/MAGE-C2 cancer-testis antigen is frequently expressed in advanced prostate cancer, indicates a higher risk for biochemical recurrence (i.e., increase in PSA values) after radical surgery, and could, therefore, potentially serve as a marker of tumor progression that can help predict a patient’s clinical course and assist doctors in making treatment decisions.
  • Two CRI postdoctoral fellows at the University of California, San Diego, Xiaoyuan Song, Ph.D., and Chunyu Jin, Ph.D., both in the laboratory of Michael G. Rosenfeld, M.D., found a protein that is involved both in inhibiting androgen receptor target genes, such as prostate-specific antigen (PSA), as well as in regulating the inflammatory properties of innate immune cells called macrophages.
  • Peter Savage, Ph.D., a CRI investigator at the University of Chicago, obtained the first direct insight into the basic biology of tumor-infiltrating regulatory T cells in a model of prostate cancer.
  • CRI Investigators Padmanee Sharma, M.D., Ph.D., and Sumit Subudhi, M.D., Ph.D., of MD Anderson Cancer Center, have conducted innovative studies testing the effects and immune correlates of responses in patients with advanced prostate cancer treated with anti-CTLA-4 checkpoint blockade.
  • In 2019, the CRI Anna-Maria Kellen Clinical Accelerator in collaboration with the Parker Institute for Cancer Immunotherapy launched a prostate cancer platform clinical trial evaluating different treatment combinations including the PD-1 inhibitor nivolumab.

See what prostate cancer-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way cancer is treated, forever—curing more people and saving more lives.

Donate to prostate cancer research

Featured Patient

Going to the Internet and typing in ‘advanced prostate cancer’ is like drinking from a fire hose.

Joe B
Prostate Cancer  |  Diagnosed
Read My Story
Featured Scientist
Michel Sadelain, M.D., Ph.D.
Memorial Sloan Kettering Cancer Center
Grantee  |  2013
View Funding Profile

Prostate Cancer Statistics

2nd Most common cancer in men worldwide
1.3 Million newly diagnosed patients each year globally
4% Of all cancer-related deaths caused by prostate cancer
99% Of prostate cancers found in local or regional stages

Prostate Cancer Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new prostate cancer treatments. Use this information to consider your clinical trial options.

  • Targeted Antibodies
  • Cancer Vaccines
  • Adoptive Cell Therapy
  • Immunomodulators
  • Oncolytic Virus Therapy

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers on cancer cells, in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in prostate cancer clinical trials include:

  • Angiopoietin: this pathway can promote the growth of blood vessels in tumors
  • DLL/Notch: a pathway that can promote cell growth
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • TROP2: a protein that is commonly overexpressed in cancer and appears to aid cancer cell self-renewal, proliferation, invasion, and survival
  • VEGF/VEGF-R: a pathway that can promote blood vessel formation in tumors

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in prostate cancer clinical trials include:

  • 5T4: an antigen often expressed by several different types of cancers
  • CEA: a protein involved in cellular adhesion that is normally produced only before birth, but is often abnormally expressed in cancer and may contribute to metastasis
  • PAP: an enzyme made by prostate cells that is often overproduced by prostate tumors
  • Personalized neoantigens: these abnormal proteins arise from mutations and are expressed exclusively by tumor cells
  • PSA: an enzyme made by prostate cells that is often overproduced by prostate tumors
  • PSMA: a surface protein found on prostate cells that is often overexpressed by prostate cancer cells
  • Survivin: a protein that can prevent cellular death and is overexpressed by a number of cancer cell types
  • Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels

Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in prostate cancer clinical trials include:

  • PSCA: a surface protein that is found on several cell types and is often overexpressed by cancer cells
  • PSMA: a surface protein found on prostate cells that is often overexpressed by prostate cancer cells

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in bladder cancer clinical trials include:

  • CD73 or A2AR: blocking these pathways can help prevent the production of immunosuppressive adenosine
  • CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
  • ICOS: activating this co-stimulatory pathway on T cells can help enhance immune responses against cancer
  • IDO: blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
  • LAG3: blocking this pathway may be able to help prevent suppression of cancer-fighting T cells
  • OX40: activating this co-stimulatory pathway can help promote T cell survival after activation
  • PD-1/PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted,” and can restore the activity of already-exhausted T cells
  • Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors

Oncolytic virus therapy uses viruses that are often, but not always, modified in order to infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in prostate cancer clinical trials include:

  • Adenovirus: a family of common viruses that can cause a wide range of typically mild effects including sore throat, fatigue, and cold-like symptoms
  • Herpes simplex virus: a virus that can cause the formation of sores on the mouth and genitals
  • Reovirus: a family of viruses that can affect the gastrointestinal and respiratory tracts in a range of animal species
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Sources: ACS Facts and Figures 2020; CA: A Cancer Journal for Clinicians (DOI: 10.3322/caac.20107);; CRI documents; GLOBOCAN 2018; National Cancer Institute (NCI); NCI Physician Data Query (PDQ); National Comprehensive Cancer Network (NCCN) Guidelines for Patients; Oncoimmunology (DOI: 10.4161/onci.24523)

Updated August 2020

*Immunotherapy results may vary from patient to patient. Consult a healthcare professional about your treatment options.

*Immunotherapy results may vary from patient to patient.