Immunotherapy Articles

BERKELEY, CA (UroToday.com) - Presently, despite immunotherapy with bacillus Calmette-Guérin (BCG) - which represents the gold standard adjuvant treatment of non-muscle invasive bladder cancer (NMIBC) - the optimal dose, schedule of instillations, and the ideal strain still remain undefined.

Recently developed immunotherapeutic agents, like anti-cytotoxic T lymphocyte antigen 4 antibody (CTLA4), anti-programmed cell death 1 (PD1) or anti-programmed cell death-ligand 1 (PDL1), have demonstrated substantial potential for the treatment of a variety of malignancies.

Immune checkpoint inhibitors (ICI) have dramatically changed the face of cancer treatment and are gaining in importance. The ICIs have now been approved for the treatment of advanced cancers, including melanoma, non-small-cell and small cell lung cancers, renal cell carcinoma, Hodgkin's lymphoma, head and neck cancers and urothelial carcinoma and further indications are to be expected.

Management of genitourinary (GU) cancers is improving rapidly with the development of immunotherapy agents, especially anti-PD-1/anti-PD-L1 therapies. Large studies have shown better outcomes for the treatment of these patients, leading to new drug approvals and recent changes in standards of care in renal, prostate and bladder cancer.

Prostate cancer (PCA) seems to be more of an immunologic desert than other tumor entities. It is striking that only rarely does prostate cancer show abundant immune cells and a proimmunogenic microenvironment.

Nivolumab, an anti-PD1 immune control point inhibitor, is the first treatment that has improved the overall survival of patients after first-line metastatic renal cell carcinoma in 2015. Over the past two years, a large number of trials on these treatments and the interest of associations are being evaluated.

The algorithms for treatment of metastatic cancers are evolving due to positive results obtained with immunotherapy. Therapeutics approaches to stimulate the immune system have already been used in the treatment of kidney and bladder cancer, such as the administration of cytokines and BCG therapy, confirming the immunogenicity of these tumors.

In the last few years, significant progress has been achieved in the therapeutic options for advanced urothelial bladder cancer.

The aim of this work was to give an overview of the status and future perspective of the therapeutic options in this setting.

The annual symposium of the German Research Association for Bladder Carcinoma (DFBK) was organized on February 7th and 8th, 2020, in Düsseldorf. On the first day, eight international guest speakers invited by the DFBK and the Department of Urology of the Heinrich Heine University Düsseldorf presented the current state of research on bladder cancer (BC).

Improved understanding of the immunomodulatory interactions between tumor cells and immune cells has led to new and promising systemic therapeutic approaches in the first- and second-line therapy of urological tumors.

Therapeutic intervention using oncolytic viruses is called virotherapy. This type of virus is defined by the ability to replicate in tumor cells only and to destroy these cells upon replication. In addition, this virus type is able to induce a tumor-directed immune response.

Prostate cancer is the second most common malignant neoplasm in men worldwide and the fifth cause of cancer-related death. Although multiple new agents have been approved for metastatic castration resistant prostate cancer over the last decade, it is still an incurable disease.

The treatment paradigm of advanced renal cell carcinoma (RCC) has changed rapidly in recent years. In first-line treatment of intermediate- to poor-risk patients, the CheckMate 214 study demonstrated a significant survival advantage for nivolumab and ipilimumab versus sunitinib.

Background: Renal cell carcinoma (RCC) is the most common type of renal malignancy with 87% frequency. As a global health problem, kidney cancer is responsible for 2.

The CRISPR-based technology has revolutionized genome editing in recent years. This technique allows for gene knockout and evaluation of function in cell lines in a manner that is far easier and more accessible than anything previously available.

Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.

Nivolumab is approved for mRCC patients who have received prior anti-angiogenic therapy but the duration of therapy required for sustained clinical benefit is unknown. A phase II clinical trial to investigate the feasibility of intermittent nivolumab dosing was conducted.

Bacillus Calmette-Guerin (BCG) is widely used as an immunotherapeutic agent and recommended in management of non-muscle-invasive bladder cancer (NMIBC). There is no consensus on the optimal dose of the BCG.

This study investigated the effect of metronomic cyclophosphamide (CPA) in combination with personalized peptide vaccination (PPV) on regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), and whether it could improve the antitumor effect of PPV.

The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990.

Immunotherapies for cancer are transforming patient care, but clinical responses vary considerably from patient to patient. Simple, inexpensive strategies to target treatment to likely responders could substantially improve efficacy while simultaneously reducing health care costs, but identification of reliable biomarkers has proven challenging.

Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S.

We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations.

Several drugs have demonstrated clinical activity in metastatic renal cell carcinoma (mRCC). The identification of key metabolic pathways has led to the development of novel targeted therapies which have drastically changed the treatment paradigm of mRCC.

Clear cell carcinoma is the most common form of renal cell carcinoma (RCC). Metastatic RCC is poorly responsive to treatment and has a bleak prognosis. Newer systemic agents have improved outcomes. Furthermore, their interaction with radiation treatment (RT) may provide further therapeutic options.

The outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients.

Introduction: Upper tract urothelial carcinoma (UTUC) remains a complex disease to manage given challenges in staging, surgical resection, use of perioperative therapy, and prevention of bladder recurrences.

Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas.

Urothelial bladder cancer displays a high number of somatic mutations that render these tumors more responsive to immunotherapy. Several immunotherapeutic agents were examined in patients with advanced stage urothelial bladder cancer and recently atezolizumab - an (PDL-1) immune checkpoint inhibitor antibody - was approved for the treatment of patients with metastatic disease progressing after platinum combination therapy.

One of the major challenges of personalized oncology lies in identifying predictive biomarkers of response to therapy that are practical in the clinical setting. Although many new targeted and immune-based treatments have emerged in recent years as effective systemic therapy options in metastatic renal cell carcinoma (mRCC), optimizing the selection and sequencing of treatments for any individual patient with this disease remains a significant challenge.

M7824 (MSB0011359C) is a novel first-in-class bifunctional fusion protein consisting of a fully human IgG1 anti-PD-L1 monoclonal antibody (with structural similarities to avelumab) linked to the extracellular domain of two TGFβ receptor 2 (TGFβR2) molecules serving as a TGFβ Trap.

BERKELEY, CA (UroToday.com) - Sipuleucel-T, an autologous cellular immunotherapy, was approved by the US FDA in 2010 with the indication for use in men with metastatic castrate-refractory prostate cancer with the clinically defined disease parameters of minimal or absent symptoms of metastasis.

Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin.

Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors is the current first-line treatment in metastatic renal cell carcinoma (mRCC). Immunotherapy with checkpoint inhibitor has been recently added to the armamentarium of mRCC treatment.

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is used for the treatment of bladder cancer. The recruitment of neutrophlis to the bladder after BCG instillation exerts anti-tumor activity against bladder tumor.

The treatment of advanced metastatic urothelial carcinoma has recently evolved with the approval of five checkpoint inhibitors. In the second-line setting, in patients who have progressed on cisplatin-based chemotherapy, pembrolizumab, atezolizumab, durvalumab, nivolumab and avelumab are United States Food and Drug Administration (FDA) approved.

To propose and validate a new approach to stratify clinically staged organ-confined muscle-invasive bladder cancer patients (cT2N0M0) that are pathologic non-responders to neoadjuvant chemotherapy (NAC) to better characterize NAC non-response.

Until recently, there has been little advancement in the management of invasive and metastatic urothelial cancer in over 30 years, and outcomes with cisplatin-based chemotherapy remain unchanged. Inhibitors targeting PD-1 signaling on cytotoxic T-cells have revolutionized bladder cancer therapy leading to durable responses.

Metastatic bladder cancer is an aggressive malignancy with a poor prognosis when presenting with advanced stage. Cisplatin-based therapy has been the mainstay of first-line treatment but therapy in second-line setting has been an unmet medical need for decades.

In recent years, immunotherapy has come to the forefront as a major development in cancer treatment. Evasion of the immune system by tumor cells has been identified as one of the hallmarks of cancer and multiple therapies have been developed to counter this process.

SAN DIEGO, CA USA (UroToday.com) - Presented by Neal Shore, MD, FACS at the American Urological Association (AUA) Annual Meeting - May 4 - 8, 2013 - San Diego Convention Center - San Diego, California USA

SAN DIEGO, CA USA (UroToday.com) - Presented by E. David Crawford, MD,¹ Adam S. Kibel, MD,² and Neal D.Shore, MD, FAC ³ at the American Urological Association (AUA) Annual Meeting - May 4 - 8, 2013 - San Diego Convention Center - San Diego, California USA

SAN DIEGO, CA USA (UroToday.com) - Presented by Thomas Gardner,¹ Daniel Petrylak,² John Corman,³ Simon Hail,⁴ Ralph Weinstein,⁵ Robert Sims,⁶ Todd DeVries,⁶ and Celestia Higano⁷ at the American Urological Association (AUA) Annual Meeting - May 4 - 8, 2013 - San Diego Convention Center - San Diego, California USA

SAN DIEGO, CA USA (UroToday.com) - Presented by Matthew R. Cooperberg, MD,¹ Oliver Sartor, MD,² Christopher Pieczonka, MD,³ Raoul S. Concepcion, MD, FACS,⁴ Vahan Kassabian, MD,⁵ Ronald Tutrone, MD, FACS, CPI,⁶ James Bailen, MD,⁷ Neal Shore, MD, FACS,⁸ Lawrence Karsh, MD, FACS,⁹ Bernard Hertzman, MD,¹⁰ David Penson, MD, MPH,¹¹ Candice Mccoy, MD,¹² Andrew Sandler, MD,¹² Robert Tyler, PhD,¹² James Whitmore, PhD,¹² and Celestia S. Higano, MD¹³ at the American Urological Association (AUA) Annual Meeting - May 4 - 8, 2013 - San Diego Convention Center - San Diego, California USA

Metastatic urothelial carcinoma (UC) remains an aggressive disease associated with limited treatment options and a reduced survival. In spite of this, the first-line treatment based on platinum-based combinations has remained virtually unchanged for the last 20-30 years.

Physicians treating patients affected by nonmuscle-invasive bladder cancer (NMIBC) have been in shock during the last six years since manufacturing restrictions on the production of the first-option medicine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), have resulted in worldwide shortages.

In the past 40 years, intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been carried out as the most effective treatment for preventing local recurrences and tumor progression of non-muscle-invasive bladder cancer.

Bacillus Calmette-Guerin (BCG) is one of the most effective treatments for bladder cancer. Little attention has been paid to the possible role of neutrophils in BCG immunotherapy. In this study, we examined neutrophil extracellular traps (NETs) formation induced by BCG stimulation, and found that BCG-induced NETs exerted cytotoxicity, induced apoptosis and cell-cycle arrest, and inhibited migration in bladder tumor cells.

The clinical application of PD1/PD-L1 targeting checkpoint inhibitors in colorectal cancer (CRC) has largely focused on a subset of microsatellite instable (MSI-high) patients. However, the proposed genotype that sensitizes these patients to immunotherapy is not captured by MSI status alone.

BERKELEY, CA (UroToday.com) - It seems to have become a recurring theme of discussion among urologists that intravesical bacillus Calmette-Guérin (BCG) immunotherapy, while effective in a certain population of patients, can also be seen as simply delaying the inevitable in another subgroup of patients.