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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Immunotherapies in Early and Advanced Renal Cell Cancer
Abstract:
The development of new immunomodulatory monoclonal antibodies targeting the CTLA-4 or PD-1 axis has led to a revival of research on immunotherapies in solid tumours including renal cell cancer (RCC). The initial results observed with these monoclonal antibodies in the treatment of advanced melanoma have resulted in considerable interest in this treatment strategy in all tumour types. Preliminary data of these new antibodies in advanced RCC are promising and they have good safety profiles. Response rates are low but durable tumour control has been observed in some patients. However, at the moment there is no evidence that targeting the CTLA-4 or PD-1 axis provides a substantial clinical benefit compared to established treatment with tyrosine kinase or mTOR inhibitors. There are also no reliable predictive markers. At the moment, several randomised trials have been initiated to investigate the new immunomodulatory antibodies either as single agents or in combination with anti-VEGF targeted therapy. Vaccines have continued to be investigated in advanced and adjuvant settings. No trial has so far established vaccines as a standard treatment in either situation. There are still large randomised trials ongoing investigating the potential benefit of a vaccine in combination with standard tyrosine kinase inhibitor therapy. In this chapter we will summarise selected studies on immunotherapy in advanced RCC with a focus on anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies. We will also touch briefly on the adjuvant situation and tumour vaccines.
Insights
New immunotherapies, including antibodies targeting CTLA-4 and PD-1, show promise for advanced renal cell cancer (RCC). While durable tumor control is observed, further trials are needed to confirm clinical benefit over existing treatments.
Area of Science:
- Oncology
- Immunology
Background:
- Immunotherapy research is revitalized in solid tumors, including renal cell cancer (RCC).
- Monoclonal antibodies targeting the CTLA-4 and PD-1 pathways are of significant interest.
- Initial data in advanced RCC show promising safety profiles for these novel agents.
Purpose of the Study:
- To summarize immunotherapy studies in advanced RCC.
- To focus on anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies.
- To briefly discuss adjuvant settings and tumor vaccines.
Main Methods:
- Review of selected studies on immunotherapy in advanced RCC.
- Focus on anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies.
- Brief consideration of adjuvant therapies and tumor vaccines.
Main Results:
- Preliminary data for new immunomodulatory antibodies in advanced RCC are promising with good safety.
- Response rates are low, but durable tumor control is noted in some patients.
- No current evidence shows substantial clinical benefit over tyrosine kinase or mTOR inhibitors; predictive markers are lacking.
Conclusions:
- Randomized trials are underway to evaluate immunomodulatory antibodies as single agents or in combination with anti-VEGF therapy.
- Vaccine research continues, but none are established as standard treatment.
- Further investigation is required to establish the role of immunotherapy in RCC treatment.
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