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The identification of renal cell carcinoma as a target for allogeneic based cancer immunotherapy
Richard W Childs1, Takehito Igarashi
1National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892, USA. childsr@nih.gov
Abstract:
Renal cell carcinoma tumor cells are intrinsically resistant to chemotherapy, but unlike most solid tumors, may be susceptible to immune-based therapy. Because powerful immune effects can be generated against hematological malignancies following allogeneic stem cell transplantation, we investigated for similar anti-tumor responses in patients with metastatic renal cell carcinoma following the transplantation of an allogeneic immune system from a healthy HLA-matched family donor. Early laboratory and clinical results have demonstrated that following a reduced-intensity allogeneic stem cell transplant, donor T-cell mediated anti-tumor effects, resulting in sustained and sometimes complete tumor regression, can be generated against renal cell carcinoma (RCC) refractory to conventional cytokine-based therapy. Early data indicate that cytotoxic T cells of donor origin are the mediators of these anti-tumor effects. These preliminary studies provide additional evidence supporting the susceptibility of RCC to immune attack and lay the foundation for future targeted allo-immune-based cancer strategies.
Insights
Allogeneic stem cell transplantation can induce donor T-cell responses against renal cell carcinoma (RCC). This immune attack leads to tumor regression in patients with metastatic RCC, suggesting new cancer treatment strategies.
Area of Science:
- Oncology
- Immunology
- Hematology
Background:
- Renal cell carcinoma (RCC) exhibits intrinsic resistance to traditional chemotherapy.
- Solid tumors, including RCC, may be susceptible to immune-based therapies.
- Allogeneic stem cell transplantation (allo-SCT) effectively generates immune responses against hematological malignancies.
Purpose of the Study:
- To investigate the potential of allo-SCT to elicit anti-tumor responses in patients with metastatic RCC.
- To explore the efficacy of a healthy, HLA-matched family donor immune system in treating refractory RCC.
- To determine if similar anti-tumor effects observed in hematological cancers can be achieved in RCC.
Main Methods:
- Patients with metastatic renal cell carcinoma received a reduced-intensity allogeneic stem cell transplant from an HLA-matched family donor.
- Laboratory and clinical assessments were conducted to monitor anti-tumor responses.
- Analysis focused on identifying the immune mediators responsible for tumor regression.
Main Results:
- Reduced-intensity allo-SCT generated significant anti-tumor effects against RCC.
- Sustained and complete tumor regression was observed in some patients.
- Donor T cells were identified as the primary mediators of these anti-tumor effects.
- These responses occurred in RCC refractory to conventional cytokine therapy.
Conclusions:
- RCC is susceptible to immune attack, particularly from donor T cells post-allo-SCT.
- Allogeneic transplantation can induce potent anti-tumor immunity against renal cell carcinoma.
- These findings support the development of targeted allo-immune-based strategies for RCC treatment.