DC1s-CTL Cellular Therapy for Renal Cell Carcinoma

Study Overview
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Brief Summary
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This trial is to evaluate the safety and effectiveness of autologous type-1 polarized dendritic cell vaccines (patients' autologous DC1s loaded with multiple antigens CTL epitope peptide complexes), after radical resection for patients with stage III-IV renal cell carcinoma. Autologous cytotoxic of T lymphocytes (CTL) induced by type-1 polarized dendritic cells (DC1) loaded with MAGE-3/MAGE-4/survivin/ her2 /COX-2 CTL epitope peptides .

Detailed Description
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All participants judged to have RCC and considered able to conduct apheresis. Immunotherapy regimen will include subcutaneous injection (3million cells) DC1 vaccines and intravenous infusion CTL cells. On day 0,participants conduct apheresis for 50-60ml. PBMCs were separated from paiticipants by density gradient centrifugation. The adherent cells were initiated into DC followed by the particular combination of cytokines to promote DC type-1 polarization. On day 6, the synthetic CTL epitope peptides were added into the culture for autologous DCs for another 24h. Then one half of DC1s were resuspended in 1ml normal saline for clinical multi-point injection near lymph nodes. The remaining half were cocultured with autologous T cells for another 7 days to induce antigen-specific CTL cells. The applied TAAs included MAGE-3/ MAGE-4/ survivin/ her2 /ect. On day 14, after quality inspection qualified, CTL cells were harvested and resuspended in 100ml normal saline and 2% autologous plasma for clinical intravenous infusion, once a day for 3 days. In order to avoid overlap between experimental immunotherapy and potential adjuvant chemotherapy, chemotherapy may start at least 2 weeks after completion of the cycle of immunotherapy. The 2nd cycle of immunotherapy may start at least 4weeks after the completion of chemotherapy.

Official Title
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DC1s-CTL Cell Therapy to Treat Patients With Renal Cell Carcinoma After Radical Resection

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Biological: DC1-CTL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed stage III-IV renal malignancies; The patient underwent radical operation of RCC within 8 weeks before enrollment; Must have normal marrow hematopoiesis function as defined below: Hemoglobin≥90g/L, WBC>4000/mm3, Absolute Neutrophil Count (ANC)≥1500/µL, Platelet≥ 100,000/µL, Must have normal important organ function as defined below: Total bilirubin≤1.5 x institutional upper limit of normal(ULN), AST(SGOT) and ALT(SGPT)≤2.5x ULN , ALP≤1.5x ULN; BUN and Creatinine <1.5x ULN, Creatinine clearance ≥80mL/min. life expectancy≥3 months; No other serious heart, liver and kidney organ dysfunction; Quality of life score (Karnofsky performance score) ≥60; Patients must be able to understand and be willing to sign a written informed consent document. Exclusion Criteria: Prior allergic reaction or hypersensitivity to cytokines (eg.IL-2); Patients with systemic or local infection requiring anti-infectious treatment; Patients currently treated with systemic immunosuppressive agents, including steroids, Patients with active autoimmune disease or history of transplantation requiring steroid treatment; Tested positive for HIV; Pregnant or lactating women Patients with important organ dysfunction; Any reason that, in the opinion of the investigator, contraindicates that the patient participates in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dendritic cell vaccine<br>DC1-CTL cellular therapy | Biological: DC1-CTL<br>* Autologous cytotoxic of T lymphocytes (CTL) were induced by type-1 polarized dendritic cells (DC1) loaded with MAGE-3/MAGE-4/survivin/ her2 /COX-2 CTL epitope peptides .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Our primary objective is to evaluate whether our cellular therapy regimen is safe. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| G250 mRNA figures |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dendritic cells, cytotoxic T lymphocyte, DC vaccine