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.

Therapeutic approaches for treatment of urothelial transitional cell carcinoma based on immune system modulation, as well as the contribution of intravesica Bacillus de Calmette-Guérin (BCG) and the recentin corporation of checkpoint inhibitors had found irrefutable proofs of concept for the indication of antitumoral immunontherapy in such 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).

The approval of the PD‑1 and PD-L1 (programmed cell death [ligand] 1) antibodies pembrolizumab, nivolumab, and atezolizumab has fundamentally changed the therapeutic landscape of locally advanced or metastatic urothelial carcinoma.

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.

Penile cancers are rare, the vast majority is represented by squamous cell carcinoma, with HPV virus being found in 30 to 40% of cases. At a locally advanced or metastatic stage, first-line treatment relies on platinum and taxane based polychemotherapy.

Chronic recurrent bacterial prostatitis (HRBP) affects the reproductive function and negatively affects the quality of life of men. The multifactorial pathogenesis of this disease causes the failure of antibiotic therapy and some cases, requires an in-depth study of the mechanisms of disease development and additional treatment methods.

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.

Despite initial promising results, the IMvigor211 clinical trial failed to demonstrate an overall survival (os) benefit for atezolizumab compared with chemotherapy as second-line treatment for metastatic bladder cancer (mbc).

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.

While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1).

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.

Inhibition of the programmed cell death protein 1 (PD-1) pathway has demonstrated clinical benefit in metastatic urothelial cancer (mUC); however, response rates of 15% to 26% highlight the need for more effective therapies.

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.

Since sipuleucel-T approval in 2010, the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) now includes the androgen-receptor signaling pathway inhibitors (ASPIs) abiraterone acetate or enzalutamide.

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.

The role of immune checkpoint inhibition (ICI) in the treatment of prostate cancer (PC) still remains elusive. It has been proposed that combination of ICI with other molecules increases the efficacy of immunotherapy in PC.

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.

Background Metastatic Squamous cell Penile Carcinoma (mSCPC) is an orphan disease with a virally induced oncogenesis. PD-L1 expression rate is around 60% with a strong correlation between PD-L1 in the primary tumour and metastases.

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.

Immune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab have improved outcomes in metastatic renal cell carcinoma (mRCC) patients, but they are also associated with immune-related adverse events (irAEs).

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.

Tumor-infiltrating lymphocyte (TIL) therapy is a personalized cancer treatment which involves generating ex vivo cultures of tumor-reactive T cells from surgically resected tumors and administering the expanded TILs as a therapeutic infusion.

This article reviews the use of adjuvant therapies for prevention of recurrence following resection of clinically localized renal cell carcinoma (RCC). Clinical trials evaluating adjuvant therapy for RCC have focused primarily on the use of tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, which had improved outcome in patients with metastatic disease.

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.

Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). Pivotal studies evaluating immune checkpoint inhibitors mostly excluded nccRCC. The aim of this retrospective and multicentre study was to evaluate the activity of programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors specifically in metastatic pRCC.