DC1s-CTL Cellular Therapy for Renal Cell Carcinoma

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

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 .

Study Overview

• Status: Unknown
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Biological: DC1-CTL

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Junnian Zheng, MD; Phone Number: 86-0516-83372010; Email: jnzheng@xzmc.edu.cn
• Study Contact Backup: Name: Huizhong Li, MM; Phone Number: 86-0516-85582635; Email: lhz@xzmc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dendritic cell vaccine; DC1-CTL cellular therapy	Biological: DC1-CTL; 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 .

What is the study measuring?

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	Time Frame
G250 mRNA figures	24 weeks

Other Outcome Measures

Outcome Measure	Time Frame
T cell subsets figures	12 weeks
Serum cytokine secretion figures	12 weeks

Collaborators and Investigators

• Sponsor: Xuzhou Medical University
• Investigators: Principal Investigator: Junnian Zheng, MD, Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Anticipated): August 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: May 26, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (Estimate): June 1, 2016

Study Record Updates

• Last Update Posted (Estimate): June 2, 2016
• Last Update Submitted That Met QC Criteria: May 31, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: dendritic cells; DC vaccine; cytotoxic T lymphocyte
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: XYFY2016-KL012-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No