sipuleucel-T

For centuries, therapeutic cancer vaccines have been developed and tried clinically. Way back in the late 19th century, the Father of Immunotherapy, William Coley had discovered that bacterial toxins were effective for inoperable sarcomas. In the 1970s, the Bacillus Calmette-Guérin (BCG) vaccine was repurposed, e.g ., for advanced melanomas. Then, therapeutic cancer vaccines based on tumor-associated antigens (found on the surfaces of cancer cells) were tried clinically but apparently have not made a really significant clinical impact...

Due to its slow progression and susceptibility to radical forms of treatment, low-grade PC is associated with high overall survival (OS). With the clinical progression of PC, the therapy is becoming more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by e.g., immune evasion through Treg cells, synthesis of immunosuppressive mediators, and the defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of tumors and eliminate the immunosuppressive properties of the TME...

Immunotherapy remains to be an appealing treatment option for prostate cancer with some documented promise. Prostate cancer is traditionally considered as an immunologically "cold" tumor with low tumor mutation burden, low expression of PD-L1, sparse T-cell infiltration, and a immunosuppressive tumor microenvironment (TME). Sipuleucel-T (Provenge) is the first FDA approved immunotherapeutic agent for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC); demonstrating a benefit in overall survival...

ConspectusCancer vaccines provide an efficient strategy to enhance tumor-specific immune responses by redeploying immune systems. Despite the approval of the first cancer vaccine (Sipuleucel-T) by the U.S. Food and Drug Administration in 2010, most therapeutic cancer vaccines fail in clinical trials. Basically, tumor-specific immune responses rely on not only T-cell but also B-cell immunity, which indicates that cancer vaccines should leverage both arms of the adaptive immune system. For example, CD8+ T cells activated by antigen-presenting cells (APCs) recognize and directly kill tumor cells via peptide-bound major histocompatibility complex (pMHC)...

(1) Background: The COVID-19 pandemic has led to the fast-tracked development of vaccines under emergency use authorization. In light of the growing concerns about fast-tracked vaccines, this article reviews the safety, efficacy, and lessons learned of previously fast-tracked vaccines. (2) Methods: An article search regarding the safety and efficacy of fast-tracked vaccines was done in PubMed, Embase, Web of Science, and ScienceDirect. Of the 104 results, 24 articles were included. Five articles about BiovaxID, THERATOPE® , Sipuleucel-T, and AIDSVAX were also reviewed...

INTRODUCTION: Despite FDA approval of sipuleucel-T in 2010, endeavors to use immune checkpoint inhibitors in unselected prostate cancer patients have not improved clinical outcomes. These efforts include studies with anti-PD1/PD-L1 and anti-CTLA-4 alone and in combination with existing standards of care. These strategies are generally T-cell centric and disregard the broader complex and pleiotropic components of the prostate cancer tumor microenvironment such as natural killer cells, myeloid-derived suppressor cells, and tumor-associated macrophages...

Prostate cancer is one of the most common malignant tumors in men. Initially, it is androgen-dependent, but it eventually develops into castration-resistant prostate cancer (CRPC), which is incurable with current androgen receptor signaling target therapy and chemotherapy. Immunotherapy, specifically with immune checkpoint inhibitors, has brought hope for the treatment of this type of prostate cancer. Approaches such as vaccines, adoptive chimeric antigen receptor-T (CAR-T) cells, and immune checkpoint inhibitors have been employed to activate innate and adaptive immune responses to treat prostate cancer, but with limited success...

The treatment landscape for metastatic castration-resistant prostate cancer has evolved extremely in recent years and several drug classes are now available. Nonetheless, the lack of validated predictive biomarkers makes therapeutic choice and the best sequential approach difficult. The location of the metastatic site could be a valid criterion for choosing among the treatment options available. Although bone remains the most frequent metastatic site and a possible target for many drugs, recent data suggest a profound shift in the disease spectrum with visceral metastases increasing incidence...

Immunotherapy, which stimulates the body's immune system, has received a considerable amount of press in recent years because of its powerful benefits. Cancer immunotherapy has shown long-term results in patients with advanced disease that are not seen with traditional chemotherapy. Immune checkpoint inhibitors, cytokines like interleukin 2 (IL-2) and interferon-alpha (IFN), and the cancer vaccine sipuleucel-T have all been licensed and approved by the FDA for the treatment of various cancers. These immunotherapy treatments boost anticancer responses by stimulating the immune system...

(1) We hypothesized that adding concurrent stereotactic ablative radiotherapy (SAbR) would increase the time to progression in patients with metastatic castrate-resistant prostate cancer (mCRPCA) treated with sipuleucel-T. (2) Patients with a history of prostate cancer (PC), radiographic evidence of metastatic disease, and rising prostate-specific antigen (PSA) > 0.2 ng/dL on castrate testosterone levels were enrolled in this single-arm phase II clinical trial and treated with sipuleucel-T and SAbR. The primary endpoint was time to progression (TTP)...

Cancer immunotherapy, or the utilization of components of the immune system to target and eliminate cancer, has become a highly active area of research in the past several decades and a common treatment strategy for several cancer types. The concept of harnessing the immune system for this purpose originated over 100 years ago when a physician by the name of William Coley successfully treated several of his cancer patients with a combination of live and attenuated bacteria, later known as "Coley's Toxins", after observing a subset of prior patients enter remission following their diagnosis with the common bacterial infection, erysipelas...

BACKGROUND: Current treatments for castrate (hormone)-resistant prostate cancer (CRPC) remain limited and are not curative, with a median survival from diagnosis of 23 months. The PAP-specific Sipuleucel-T vaccine, which was approved by the FDA in 2010, increases the Overall Survival (OS) by 4 months, but is extremely expensive. We have previously shown that a 15 amino accid (AA) PAP sequence-derived peptide could induce strong immune responses and delay the growth of murine TRAMP-C1 prostate tumors...

IMPORTANCE: The federal Hospital Price Transparency final rule, which became effective in 2021, requires hospitals to publicly disclose payer-specific prices for drugs. However, little is known about hospital markup prices for parenterally administered therapies. OBJECTIVE: To assess the extent of price markup by hospitals on parenterally administered cancer therapies and price variation among hospitals and between payers at each hospital. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis was conducted of private payer-specific negotiated prices for the top 25 parenteral (eg, injectable or infusible) cancer therapies by Medicare Part B spending in 2019 using publicly available hospital price transparency files...

The mainstay of treatment for metastatic prostate cancer is androgen deprivation therapy (ADT). Outcomes with ADT are variable but control of hormone-sensitive prostate cancer (HSPC) can often be achieved for many years. Death from prostate cancer is usually due to the development of escape variants able to survive and proliferate in the setting of castrate levels of serum androgens (metastatic castration-resistant prostate cancer, mCRPC). Several agents can improve survival for patients with mCRPC, including chemotherapy, agents to reduce androgen receptor signalling, the radioisotope radium-223 dichloride, and cellular immunotherapy with sipuleucel-T...

INTRODUCTION: The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) continues to evolve. Sipuleucel-T was the first immunotherapy approved by the US Food and Drug Administration (FDA) to treat asymptomatic or minimally symptomatic mCRPC. The androgen receptor-targeting agents (ARTAs) abiraterone acetate and enzalutamide were initially approved to treat mCRPC. Looking at chemotherapy-naïve men with mCRPC, we compared survival outcomes between the sipuleucel-T + ARTA cohort (men who received either sipuleucel-T or an ARTA in the first line, and then the other in the second line within 6 months) and the ARTA monotherapy cohort (men who only received ARTA monotherapy)...

BACKGROUND: Sipuleucel-T has demonstrated survival benefit in phase 3 trials but is utilized in few men with metastatic castration-resistant prostate cancer (mCRPC) in part due to low rates of PSA and objective response. Given the requirement to develop immune-mediated antitumor activity as vaccine-based therapy, sipuleucel-T may have delayed clinical activity. We explored this in a cohort of men from PROCEED (NCT01306890), an FDA-requested outcomes registry, and in a separate institutional cohort of mCRPC patients treated with sipuleucel-T at Dana-Farber Cancer Institute (DFCI)...

INTRODUCTION: Medical treatment for prostate cancer (PC) targets hormonal pathways used by malignant cells. Research advances aided in gaining knowledge about implicated molecular pathways and opened the way for establishment of new types of therapies by modifying immunological mechanisms. The aim of this review is to present completed and ongoing research projects regarding PC immunotherapy. AREAS COVERED: A literature search was conducted in PubMed/MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, and https://www...

Prostate cancer (PCa) is one of the most frequent cancer in male population. Androgen deprivation therapy is the first-line strategy for the metastatic stage of the disease, but, inevitably, PCa develops resistance to castration (CRPC), becoming incurable. In recent years, clinical trials are testing the efficacy of anti-CTLA4 on CRPC. However, this tumor seems to be resistant to immunotherapies that are very effective in other types of cancers, and, so far, only the dendritic cell vaccine sipuleucel-T has been approved...

Randomized clinical trials in oncology typically utilize time-to-event endpoints such as progression-free survival or overall survival as their primary efficacy endpoints, and the most commonly used statistical test to analyze these endpoints is the log-rank test. The power of the log-rank test depends on the behavior of the hazard ratio of the treatment arm to the control arm. Under the assumption of proportional hazards, the log-rank test is asymptotically fully efficient. However, this proportionality assumption does not hold true if there is a delayed treatment effect...

INTRODUCTION: Therapeutic cancer vaccines have been recognized as a promising treatment option in clinical oncology for nearly three decades. However, despite many efforts, only one cancer vaccine - sipuleucel-T, activating the anti-PAP (prostatic acid phosphatase) immune response, has obtained Food and Drug Administration (FDA) approval. MATERIAL AND METHODS: This review describes the most advanced research on the use of therapeutic cancer vaccines in the treatment of prostate cancer...