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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
Immunotherapy of kidney cancer
Petros D Grivas1, Bruce G Redman
1Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan School of Medicine, USA.
Abstract:
Renal cell carcinoma (RCC) accounts for 4% of all new cancer cases in males and 3% in females in the US. Compared to other solid tumors, it does not respond to traditional management modalities, such as chemotherapy and radiation therapy. However, it appears to be an immune-responsive tumor and several immunotherapeutic strategies have been investigated in the management of RCC with variable degrees of success. Active immunotherapy refers mainly to the use of vaccines, while adoptive (passive) immunotherapy includes the use of autologous immune cells, allogeneic immune cells (stem cell transplantation, donor lymphocyte infusion), as well as antibody delivery. Cytokine delivery with IL-2 has resulted in long-term disease-free survival in a small proportion of patients with metastatic disease. The continuous understanding of the mechanisms that underlie the immune complex networks has led to the identification of key molecules that play a major role in the immune response process. A panel of immuno-modulatory compounds that target such molecules has been tested in the preclinical and clinical setting. At the post-genomic era, the development of novel biomarkers can contribute to more accurate patient selection, resulting in higher responses and less toxicity of immunotherapeutic approaches.
Insights
Renal cell carcinoma (RCC) is an immune-responsive tumor, but traditional treatments are ineffective. Immunotherapy strategies, including vaccines and adoptive cell therapies, show promise for managing RCC, with ongoing research into biomarkers for better patient selection.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Renal cell carcinoma (RCC) constitutes a significant portion of cancer diagnoses in the US.
- RCC exhibits resistance to conventional treatments like chemotherapy and radiation therapy.
- RCC is recognized as an immune-responsive tumor, prompting investigation into immunotherapeutic approaches.
Purpose of the Study:
- To review the landscape of immunotherapeutic strategies for Renal Cell Carcinoma (RCC).
- To highlight the potential of active and adoptive immunotherapies in RCC management.
- To emphasize the role of understanding immune mechanisms and biomarkers in optimizing RCC treatment.
Main Methods:
- Review of existing literature on immunotherapies for RCC.
- Exploration of active immunotherapy (vaccines) and adoptive immunotherapy (cell-based therapies, antibody delivery).
- Discussion of cytokine therapy (IL-2) and immuno-modulatory compounds.
Main Results:
- Immunotherapy has shown variable success in RCC management.
- Interleukin-2 (IL-2) has achieved long-term survival in a subset of metastatic RCC patients.
- Preclinical and clinical studies are evaluating novel immuno-modulatory compounds.
Conclusions:
- Immunotherapy represents a promising avenue for RCC treatment due to its immune-responsive nature.
- Advancements in understanding immune response mechanisms are identifying key targets for novel therapies.
- Biomarker development is crucial for personalized patient selection, aiming to enhance treatment efficacy and reduce toxicity.
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