Browse
Submit Data
Databases
API
Help

Dataset Information

29 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel immunotherapy in metastatic renal cell carcinoma.

ABSTRACT: Despite the rapid development of therapeutic modalities for metastatic renal cell carcinoma (mRCC) over the past decade to include a number of targeted antiangiogenic therapies and traditional immunotherapy, such as high-dose interleukin-2 and interferon-?, mRCC continues to be associated with poor prognosis. Currently, several novel immunotherapy agents, such as cancer vaccines, adoptive cell therapy, and checkpoint inhibitors, such as programmed cell death-1 (PD-1 present on T cells), one of its ligands (PD-L1 present on antigen-presenting cells and tumor cells), and cytotoxic T-lymphocyte-associated protein-4 pathways, are being studied in mRCC and are showing promise as important steps in the management of this disease. This review summarizes the current landscape of standard and emerging immune therapeutics and other modalities for mRCC.

SUBMITTER: Cho YH

PROVIDER: S-EPMC5494344 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Novel immunotherapy in metastatic renal cell carcinoma.

Cho Yang Hyun YH Kim Myung Soo MS Chung Ho Seok HS Hwang Eu Chang EC

Investigative and clinical urology 20170620 4

Despite the rapid development of therapeutic modalities for metastatic renal cell carcinoma (mRCC) over the past decade to include a number of targeted antiangiogenic therapies and traditional immunotherapy, such as high-dose interleukin-2 and interferon-α, mRCC continues to be associated with poor prognosis. Currently, several novel immunotherapy agents, such as cancer vaccines, adoptive cell therapy, and checkpoint inhibitors, such as programmed cell death-1 (PD-1 present on T cells), one of i ...[more]

PMID: 28681030

Similar Datasets

Novel immunotherapy approaches for metastatic urothelial and renal cell carcinoma.

Project description:The treatment of metastatic renal cell carcinoma (RCC) and urothelial carcinoma (UC) remains a major challenge. Past research has implicated the immune system in tumor surveillance of both malignancies, leading to the application of immunotherapy agents for both cancers. Among them, the most promising agents are the checkpoint blockade drugs, such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death receptor 1 (PD-1), and PD-1 ligand (PD-L1). In normal physiology, these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions, which is pivotal for maintaining self-tolerance. However, tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response, leading to disease progression and metastasis. Thus, there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC. To date, nivolumab (anti-PD-1) and atezolizumab (anti-PD-L1) have been approved for the treatment of metastatic RCC and UC, respectively. Despite these successes, challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach. In this report, we review existing data and research on immunotherapy in metastatic RCC and UC.

| S-EPMC5730869 | biostudies-literature

Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review.

Project description:Localized renal cell carcinoma (RCC) is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR) inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer) has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

| S-EPMC4486756 | biostudies-literature

Complete Pathologic Responses With Immunotherapy in Metastatic Renal Cell Carcinoma: Case Reports.

Project description:Immunotherapy-based combinations have become standard of care in advanced renal cell carcinoma (RCC). Despite the potential for complete radiographic response, complete pathologic responses have been rarely reported. We present two cases of confirmed complete pathologic response to immunotherapy despite residual radiographic abnormalities. The first case describes a 68-year-old female with metastatic RCC who was treated with upfront pembrolizumab plus axitinib. She underwent nephrectomy after 15 doses of pembrolizumab with pathology revealing no evidence of viable tumor. To our knowledge, this is the first reported case of a complete pathologic response with pembrolizumab in metastatic RCC. The second case describes a 64-year-old female with metastatic RCC who was treated with second-line nivolumab after progression on cabozantinib. After 13 doses of nivolumab, she underwent nephrectomy with pathology revealing no evidence of viable tumor. These cases highlight the potential for scar tissue, fibrosis, and necrosis to persist radiographically after treatment with immunotherapy despite the absence of viable tumor cells.

| S-EPMC7783360 | biostudies-literature

The tango of immunotherapy and targeted therapy in metastatic renal cell carcinoma

Project description: Not available

| S-EPMC8797268 | biostudies-literature

The Future of Immunotherapy-Based Combination Therapy in Metastatic Renal Cell Carcinoma.

Project description:In the past two decades, there has been a significant improvement in the understanding of the molecular pathogenesis of Renal Cell Carcinoma (RCC). These insights in the biological pathways have resulted in the development of multiple agents targeting vascular endothelial growth factor (VEGF), as well as inhibitors of the mammalian target of the rapamycin (mTOR) pathway. Most recently, checkpoint inhibitors were shown to have excellent clinical efficacy. Although the patients are living longer, durable complete responses are rarely seen. Historically, high dose interleukin 2 (IL2) therapy has produced durable complete responses in 5% to 8% highly selected patients-albeit with significant toxicity. A durable complete response is a surrogate for a long-term response in the modern era of targeted therapy and checkpoint immunotherapy. Numerous clinical trials are currently exploring the combination of immunotherapy with various targeted therapeutic agents to develop therapies with a higher complete response rate with acceptable toxicity. in this study, we provide a comprehensive review of multiple reported and ongoing clinical trials evaluating the combination of PD-1/PD-L1 inhibitors with either ipilimumab (a cytotoxic T-lymphocyte-associated protein 4, CTLA-4 inhibitor) or with anti-VEGF targeted therapy.

| S-EPMC7017064 | biostudies-literature

A Phase I Study of Alpha-1,3-Galactosyltransferase-Expressing Allogeneic Renal Cell Carcinoma Immunotherapy in Patients with Refractory Metastatic Renal Cell Carcinoma.

Project description:LESSONS LEARNED:HyperAcute Renal immunotherapy was well tolerated and demonstrated antitumor activity in patients requiring salvage-line treatment for metastatic renal cell carcinoma (mRCC). HyperAcute Renal immunotherapy was safely administered with concomitant salvage-line treatments for mRCC, and it may be a candidate for inclusion in novel combinations for salvage treatment of mRCC because of its unique mechanism of action. BACKGROUND:HyperAcute Renal (HAR) immunotherapy exploits a naturally occurring barrier to xenotransplantation and zoonotic infections in humans to immunize patients against metastatic renal cell carcinoma (mRCC) cells. HAR consists of two allogeneic renal cancer cell lines genetically modified to express ?(1,3)Gal, to which humans have an inherent pre-existing immunity. METHODS:Patients with refractory mRCC were eligible for this phase I dose-escalation trial. Concomitant treatment was permitted after the initial 2 months of HAR monotherapy. HAR was injected intradermally weekly for 4?weeks then biweekly for 20?weeks, totaling 14 immunizations. The primary endpoint was safety and determination of a maximum tolerated dose (MTD). RESULTS:Among 18 patients enrolled, two grade 3 adverse events (AEs) were attributed to HAR, lymphopenia and injection site reaction, and no grade 4/5 AEs occurred. The recommended phase II dose (RP2D) was 300 million cells. One patient had a partial response and eight patients had stable disease, for a disease control rate of 50% (9/18). Median overall survival with low-dose HAR was 14.2 months and was 25.3 months with high-dose HAR. CONCLUSION:In pretreated mRCC, HAR immunotherapy was well tolerated and demonstrated antitumor activity. HAR immunotherapy may be a candidate for inclusion in novel combinations for salvage treatment of mRCC.

| S-EPMC7011628 | biostudies-literature

Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis.

Project description:PurposeMetastatic renal cell carcinoma (mRCC), as one of the most immunogenic tumors has been the focus of adoptive cellular immunotherapy (ACI), but the effects of ACI on objective response and survival in patients with mRCC are still controversial. Therefore, a systematic review and meta-analysis was performed to address this issue.MethodsA search was conducted in the PubMed database for randomized clinical trials (RCTs) with ACI in mRCC. All included articles in this study were assessed according to the selection criteria and were divided into two groups: ACI versus no ACI. Outcomes were toxicity, objective response, 1-, 3- and 5-year survival. Risk ratio (RR) and 95% confidence intervals (CI) were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by value of I(2) or P.Results4 studies (469 patients) were included. Most of ACI-related adverse reactions were grade 1 or 2 and reversible. ACI provided significant benefit in terms of objective response (RR?=?1.65; 95% CI, 1.15 to 2.38; P?=?0.007, I(2)?=?49%), 1-year survival (RR?=?1.30; 95% CI, 1.12 to 1.52; P?=?0.0008, I(2)?=?0%), 3-year survival (RR?=?2.76; 95% CI, 1.85 to 4.14; P<0.00001, I(2)?=?46%) and 5-year survival (RR?=?2.42; 95% CI, 1.21 to 4.83; P?=?0.01, I(2)?=?28%).ConclusionsACI may be a safe and effective treatment for improving objective response, 1-, 3- and 5-year survival in patients with mRCC. Besides, five obstacles for ACI, including high degree of personalization, unsuitable WHO/RECIST response criteria, inadequate identification of tumor-associated antigens (TAAs), lack of effective combination treatments and less attention paid to the quality of ACI products, should be overcome during the successful development of more potent ACI for cancer in the future.

| S-EPMC3647060 | biostudies-literature

Addition of Salvage Immunotherapy to Targeted Therapy in Patients with Metastatic Renal Cell Carcinoma.

Project description:There have been significant advances in the treatment of metastatic renal cell carcinoma (mRCC), with immunotherapy (IO)-based combinations as the standard-of-care treatment in the front-line setting. IO in this setting is paired with another IO agent or with a vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitor (TKI). One IO/IO combination and four IO/TKI combinations are currently approved. However, the role of the salvage IO in patients with disease progression on TKI monotherapy is uncertain. Here, we present a case series of five patients who were on single-agent TKI therapy for treatment-refractory mRCC and upon disease progression had an IO agent added to their TKI. The median duration of TKI monotherapy was 11.2 months (range, 1.7-31.1 months), and the median duration of response after the addition of IO was 4 months (range, 2.8-10.5 months). Although IO salvage therapy has a plausible rationale, this case series did not show a clear benefit to this approach. Further clinical trials are needed to determine the clinical utility of IO salvage therapy in mRCC.

| S-EPMC8700734 | biostudies-literature

Axitinib in Metastatic Renal Cell Carcinoma.

Project description:Targeted agents have revolutionized the management of metastatic renal cell carcinoma (RCC). Axitinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), has been an important addition to currently available therapies for advanced RCC. Its ability to inhibit VEGFRs at nanomolar concentrations distinguishes it as a potent tyrosine kinase inhibitor, with increased selectivity for VEGFR-1, 2, and 3 at clinically applicable concentrations. The phase 3 AXIS trial has established its superiority in prolonging progression-free survival (PFS) in previously treated RCC patients (median PFS 6.7 months for axitinib vs. 4.7 months for sorafenib). Common toxicities of axitinib include hypertension, diarrhea, nausea, hand-foot syndrome, fatigue, and hypothyroidism. Axitinib-induced diastolic blood pressure elevation may be associated with improved clinical outcome, likely reflecting the "on-target" effect of axitinib. Dose escalation to achieve therapeutic plasma drug levels is of considerable clinical interest. Although axitinib has established efficacy in patients treated with one previous agent, its use in the frontline setting is currently the subject of ongoing research.

| S-EPMC3873008 | biostudies-other

NK Cell-Based Immunotherapy in Renal Cell Carcinoma.

Project description:Natural killer (NK) cells are cytotoxic lymphocytes that are able to kill tumor cells without prior sensitization. It has been shown that NK cells play a pivotal role in a variety of cancers, highlighting their relevance in tumor immunosurveillance. NK cell infiltration has been reported in renal cell carcinoma (RCC), the most frequent kidney cancer in adults, and their presence has been associated with patients' survival. However, the role of NK cells in this disease is not yet fully understood. In this review, we summarize the biology of NK cells and the mechanisms through which they are able to recognize and kill tumor cells. Furthermore, we discuss the role that NK cells play in renal cell carcinoma, and review current strategies that are being used to boost and exploit their cytotoxic capabilities.

| S-EPMC7072691 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data