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Updated: Jun 6, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a
J Westermann1, A Flörcken, G Willimsky
1Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Campus Virchow-Klinikum and Campus Berlin-Buch, Berlin, Germany. joerg.westermann@charite.de
Abstract:
Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 × 10(6) interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-γ secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.
Insights
This study investigated a novel immunotherapy for metastatic renal cell cancer (RCC). While the vaccine was safe and showed some disease stabilization, it did not induce the desired immune response, suggesting challenges in overcoming tumor-induced immunosuppression.
Area of Science:
- Immunology
- Oncology
- Cancer Therapy
Background:
- Prognosis for metastatic renal cell cancer (RCC) remains poor despite targeted therapies.
- Enhancing tumor immunogenicity through genetic modification is a potential therapeutic strategy.
- Novel experimental approaches are needed for advanced RCC treatment.
Purpose of the Study:
- To assess the feasibility, safety, and efficacy of a novel vaccine in patients with metastatic clear cell RCC.
- To evaluate the immunological and clinical responses to IL-7/CD80 cotransfected allogeneic tumor cells.
- To investigate the potential of gene-modified tumor cells to overcome tumor-induced immunosuppression.
Main Methods:
- A clinical study involving 10 HLA-A(*)0201(+) patients with progressive metastatic clear cell RCC.
- Repetitive immunization over 22 weeks with IL-7/CD80 cotransfected allogeneic tumor cells (RCC26/IL-7/CD80).
- Assessment of feasibility, safety, immunological responses (cytokine profiles), and clinical responses (disease progression).
Main Results:
- Vaccination was feasible and safe in all patients.
- 50% of patients achieved stable disease, with a median time to progression of 18 weeks.
- The vaccine failed to induce TH1-polarized immune responses; instead, a TH2 profile with increased IL-10 was observed. Interferon-γ secretion was impaired, suggesting significant tumor-induced immunosuppression.
Conclusions:
- The allogeneic tumor cell vaccine (RCC26/IL-7/CD80) demonstrated safety and feasibility but did not elicit the expected antitumor immune response in metastatic RCC.
- Profound tumor-induced immunosuppression may hinder the effectiveness of this gene-modified vaccine strategy.
- Future strategies might involve vaccination in minimal residual disease settings combined with depletion of regulatory immune cells to enhance therapeutic outcomes.
