Prostate cancer immunotherapy: the path forward.
Ontology highlight
ABSTRACT: Purpose of review
To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer.Recent findings
Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease. Emerging data suggests the presence of multiple checkpoint inhibitors in the prostate cancer tumor microenvironment highlighting the need for combination immunotherapy platforms that would potentially include androgen deprivation, chemotherapy, or radiation.Summary
Preclinical and clinical data support immune-based combinations in prostate cancer and several trials are underway to better define the future of immunotherapy in prostate cancer.
SUBMITTER: Madan RA
PROVIDER: S-EPMC8258656 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:As evidenced by the recent approvals of Removab (EU, Trion Pharma) in 2009 and of Blincyto (US, Amgen) in 2014, the high potential of bispecific antibodies in the field of immuno-oncology is eliciting a renewed interest from pharmaceutical companies. Supported by rapid advances in antibody engineering and the development of several technological platforms such as Triomab or bispecific T cell engagers (BiTEs), the "bispecifics" market has increased significantly over the past decade and may occupy a pivotal space in the future. Over 30 bispecific molecules are currently in different stages of clinical trials and more than 70 in preclinical phase. This review focuses on the clinical potential of bispecific antibodies as immune effector cell engagers in the onco-immunotherapy field. We summarize current strategies targeting various immune cells and their clinical interests. Furthermore, perspectives of bispecific antibodies in future clinical developments are addressed.
| S-EPMC6698871 | biostudies-literature
Project description:The Kidney Research National Dialogue, supported by the National Institute of Diabetes and Digestive and Kidney Diseases, asked the scientific community to formulate and prioritize research objectives that would improve our understanding of kidney function and disease. High-priority objectives for AKI were identified, including enhancing training and collaborative opportunities, improving phenotyping and development of clinical tools, expanding our understanding of the pathophysiology and interaction between injury and reparative processes, and identifying determinants of long-term outcomes. Research in animal models must be translated to improve diagnosis and treatment of patients. The objectives identified by the Kidney Research National Dialogue provide the research community with future opportunities for improving the prevention, diagnosis, and treatment of people with AKI.
| S-EPMC3805072 | biostudies-literature
Project description:The interaction between the immune system and prostate cancer has been an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of 2 first-in-class proof-of-concept immunotherapies (sipuleucel-T and ipilimumab) has stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies that have garnered the most interest are the therapeutic vaccination strategies, exemplified by sipuleucel-T and PROSTVAC-VF, and immune checkpoint blockade of CTLA-4 and PD-1. Improved understanding of the immune responses generated by these strategies and development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide building blocks for future immunotherapies.
| S-EPMC3263933 | biostudies-literature
Project description:The zebrafish is a recent addition to animal models of human cancer, and studies using this model are rapidly contributing major insights. Zebrafish develop cancer spontaneously, after mutagen exposure and through transgenesis. The tumours resemble human cancers at the histological, gene expression and genomic levels. The ability to carry out in vivo imaging, chemical and genetic screens, and high-throughput transgenesis offers a unique opportunity to functionally characterize the cancer genome. Moreover, increasingly sophisticated modelling of combinations of genetic and epigenetic alterations will allow the zebrafish to complement what can be achieved in other models, such as mouse and human cell culture systems.
| S-EPMC6040891 | biostudies-literature
Project description:Immunotherapy encompasses a wide range of therapies to engage the immune system to target malignancies. In recent years, immunotherapy has made a major impact on treatment of metastatic cancer and has altered standard of care for many tumor types. However, predicting and understanding responses across tumor types has been challenging. While some metastatic cancers have shown dramatic responses to immunotherapy, such as melanoma, lung cancer, and renal cell carcinoma, prostate cancer has generally failed to show a significant response. However, small series of prostate cancer patients have shown impressive responses to cellular and immunotherapy. This review summarizes the current data for immunotherapy's use in prostate cancer, as well as how currently available data might help predict patient responses to immunotherapy. Specifically, we will review vaccine-based therapies, immune checkpoint inhibitors, and future directions that are actively being explored.
| S-EPMC7409298 | biostudies-literature
Project description:In this study, we present an intensity-modulated radiotherapy technique based on forward planning dose calculations to provide a concave dose distribution to the prostate and seminal vesicles by means of modified dynamic arc therapy (M-DAT). Dynamic arcs (350 degrees) conforming to the beam's eye view of the prostate and seminal vesicles while shielding the rectum, combined with two lateral oblique conformal fields (15 degrees with respect to laterals) fitting the prostate only,were applied to deliver doses of 78 Gy and 61.23 Gy in 39 fractions to the prostate and seminal vesicles respectively. Dynamic wedges (45 degrees of thick end, anteriorly oriented) were used with conformal beams to adjust the dose homogeneity to the prostate, although in some cases, hard wedges (30 degrees of thick part,inferiorly oriented) were used with arcs to adjust the dose coverage to the seminal vesicles. The M-DAT was applied to 10 patients in supine and 10 patients in prone positioning to determine the proper patient positioning for optimum protection of the rectum. The M-DAT was compared with the simplified intensity-modulated arc therapy (SIMAT) technique, composed of three phases of bilateral dynamic arcs. The mean rectal dose in M-DAT for prone patients was 22.5 +/- 5.1 Gy; in M-DAT and SIMAT for supine patients, it was 30.2 +/- 5.1 Gy and 39.4 +/- 6.0 Gy respectively. The doses to 15%, 25%, 35%, and 50% of the rectum volume in M-DAT for prone patients were 44.5 +/- 10.2 Gy, 33.0 +/- 8.2 Gy, 25.3 +/- 6.4 Gy, and 16.3 +/- 5.6 Gy respectively. These values were lower than those in M-DAT and in SIMAT for supine patients by 7.7%, 18.2%, 22.4%, and 28.5% and by 25.0%, 32.1%, 34.9%, and 41.9% of the prescribed dose (78 Gy) respectively. Ion chamber measurements showed good agreement of the calculated and measured isocentric dose (maximum deviation of 3.5%). Accuracy of the dose distribution calculation was evaluated by film dosimetry using a gamma index, allowing 3% dose variation and 4 mm distance to agreement as the individual acceptance criteria in prostate and seminal vesicle levels alike for all supine and prone patients. We found that fewer than 10% of the pixels in the dose distribution of the calculated area of10 x 10-cm failed the acceptance criteria. These pixels were observed mainly in the low-dose regions, particularly at the level of the seminal vesicles. In conclusion, the single-phase M-DAT technique with patients in the prone position was found to provide the intended coverage of the prescribed doses to the prostate and seminal vesicles with improved protection for the rectum. Accordingly, M-DAT has replaced non-modulated conformal radiotherapy or SIMAT as the standard treatment for prostate cancer in our department.
| S-EPMC5722620 | biostudies-literature
Project description:In the United States, prostate cancer is the most frequent malignancy in men and ranks second in terms of mortality. Although recurrent or metastatic disease can be managed initially with androgen ablation, most patients eventually develop castration-resistant disease within a number of years, for which conventional treatments (eg, chemotherapy) provide only modest benefits. In the last few years, immunotherapy has emerged as an exciting therapeutic modality for advanced prostate cancer, and this field is evolving rapidly. Encouragingly, the US Food and Drug Administration (FDA) has recently approved two novel immunotherapy agents for patients with advanced cancer: the antigen presenting cell-based product sipuleucel-T and the anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibody ipilimumab, based on improvements in overall survival in patients with castration-resistant prostate cancer and metastatic melanoma, respectively. Currently, a number of trials are investigating the role of various immunological approaches for the treatment of prostate cancer, many of them with early indications of success. As immunotherapy for prostate cancer enters its golden age, the challenge of the future will be to design rational combinations of immunotherapy agents with each other or with other standard prostate cancer treatments in an effort to improve patient outcomes further.
| S-EPMC3403579 | biostudies-other
Project description:Although most prostate cancers are localized, and the majority are curable, recurrences occur in approximately 35% of men. Among patients with prostate-specific antigen (PSA) recurrence and PSA doubling time (PSADT) less than 15 months after radical prostatectomy, prostate cancer accounted for approximately 90% of the deaths by 15 years after recurrence. An immunosuppressive tumor microenvironment (TME) and impaired cellular immunity are likely largely responsible for the limited utility of checkpoint inhibitors (CPIs) in advanced prostate cancer compared with other tumor types. Thus, for immunologically "cold" malignancies such as prostate cancer, clinical trial development has pivoted towards novel approaches to enhance immune responses. Numerous clinical trials are currently evaluating combination immunomodulatory strategies incorporating vaccine-based therapies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T cells. Other trials evaluate the efficacy and safety of these immunomodulatory agents' combinations with standard approaches such as androgen deprivation therapy (ADT), taxane-based chemotherapy, radiotherapy, and targeted therapies such as tyrosine kinase inhibitors (TKI) and poly ADP ribose polymerase (PARP) inhibitors. Here, we will review promising immunotherapies in development and ongoing trials for metastatic castration-resistant prostate cancer (mCRPC). These novel trials will build on past experiences and promise to usher a new era to treat patients with mCRPC.
| S-EPMC7831137 | biostudies-literature
Project description:In the last few years, immunotherapy has become an important cancer treatment modality, and although the principles of immunotherapy have evolved over many decades, the FDA approvals of sipuleucel-T and ipilimumab began a new wave in immuno-oncology. Despite the current enthusiasm, it is unlikely that any of the immunotherapeutics alone can dramatically change prostate cancer outcomes, but combination strategies are more promising and provide a reason for optimism. Several completed and ongoing studies have shown that the combination of cancer vaccines or checkpoint inhibitors with different immunotherapeutic agents, hormonal therapy (enzalutamide), radiotherapy (radium 223), DNA-damaging agents (olaparib), or chemotherapy (docetaxel) can enhance immune responses and induce more dramatic, long-lasting clinical responses without significant toxicity. The goal of prostate cancer immunotherapy does not have to be complete eradication of advanced disease but rather the return to an immunologic equilibrium with an indolent disease state. In addition to determining the optimal combination of treatment regimens, efforts are also ongoing to discover biomarkers of immune response. With such concerted efforts, the future of immunotherapy in prostate cancer looks brighter than ever. Clin Cancer Res; 23(22); 6764-70. ©2017 AACR.
| S-EPMC5690854 | biostudies-literature
Project description:Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.
| S-EPMC3730318 | biostudies-literature