The feasibility and dose-limiting toxicity of administering escalating doses of dendritic
cells transfected with autologous renal cell carcinoma RNA DC(DCRCC-RNA) will be defined. As
a secondary endpoint, the ability of DCRCC-RNA to induce tumor-specific immune responses
will be evaluated. Finally, the anti-tumor effects measured by clinical response criteria,
their duration and overall survival (calculated at 2-year follow-up) will be determined in
each patient receiving dendritic cell therapy.
Background: Prognosis in metastatic renal cell carcinoma is poor with a median survival of
less than one year. Although renal cell carcinoma has shown some response to immunotherapy,
the results of systemic administration of biologic response modifiers in disseminated renal
cell carcinoma have been poor. Growing evidence suggests that active immunotherapy,
particularly dendritic cells (DC) based vaccines, may prove to be a viable and clinically
effective therapeutic option for patients with advanced or metastatic renal cell carcinoma.
Methods: This study will enroll patients with renal cell carcinoma Stage III (T3 N1 M0) or
Stage IV (T4 N0 N1 M0 - any T N2 M0 - any T any N M1) after nephrectomy. Peripheral blood
mononuclear cells collected through leukapheresis are processed for DC generation.
Mononuclear cells are separated and cultured for 7 days in GM-CSF and IL-4. Harvested DC
will be pulsed with renal tumor RNA harvested during nephrectomy. An aliquot of these cells
will be tested for appropriate phenotype fungal and bacterial sterility as well as for
endotoxin content prior to lot release. Renal tumor RNA transfected DC will be stored
cryopreserved until administration.
The first 3 patients will be enrolled at a low dose and monitored for dose limiting
toxicities. If no dose limiting toxicities are seen, the next 3 patients will be enrolled at
the medium dose. If no dose limiting toxicities are seen in the medium dose, 6 additional
patients will be enrolled on the high dose and will be evaluated for dose limiting
toxicities. If in preparation of the vaccine insufficient RNA or dendritic cells are
available to perform the required three injections at the assigned dose level or if the
patient is withdrawn from the study the treatment position will remain open, i.e., no dose
fractions will be given. Patients in whom only the minimum number of DCRCC-RNA can be
produced to deliver one I.V. and one I.D. injection will be able to receive the vaccine,
even if he or she is assigned to a higher dose level, but will be replaced in order to
Data Analysis 1. To determine the short and long term toxicities associated with
administration of DCRCC-RNA in patients with metastatic RCC. 2. To determine feasibility of
DC vaccine generation according to the proportion of patients for whom sufficient cells are
generated to provide treatment. 3. To determine the cellular immune response to
administration of DCRCC-RNA. 4. To measure the clinical responses mediated by administration
- Patients with metastatic RCC following resection of the primary renal tumor
(Pathologic diagnosis and staging of the disease will be completed at time of
- Patients must have a performance status of 0 or 1 according the Eastern Cooperative
Oncology Group (ECOG) criteria and must have an estimated life expectancy of 6 months
- Patients must not have undergone any major surgery during the past 6 weeks. In
addition no chemotherapeutic agents, (standard or experimental) radiation therapy,
(local therapy or palliative treatment for painful bony metastases) or immunotherapy
(i.e. IL-2, interferon-alpha, ALT therapy) can be administered 6 weeks prior to
enrollment. Patients must have recovered from all acute toxicities from prior
- Adequate hematologic function with: WBC 3000 mm3, hemoglobin 9 mg/dl, platelets
- Patients may be transfused to meet the eligibility criteria.
- Adequate renal and hepatic function with: serum creatinine < 2.5 mg/dl, bilirubin <
- Adequate coagulation parameters with: Partial thromboplastin time < 1.5 x control
- Ability to understand and provide signed inform consent that fulfills Institutional
Review Board guidelines
- Ability to return to Duke University Medical Center for adequate follow-up as
required by this protocol.
- Women who are pregnant and nursing women are excluded.
- Patients after radical nephrectomy are excluded since no tumor tissue can be
retrieved and no vaccine generated.
- Patients with either previously irradiated or new CNS (central nervous system)
metastases as determined by enhanced cranial CT or MRI prior to enrollment.
- Patients with a history of autoimmune disease such as, but not restricted to,
inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis,
scleroderma, or multiple sclerosis.
- Patients with serious intercurrent chronic or acute illness such as pulmonary (asthma
or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness
considered by the P.I. to constitute an unwarranted high risk for investigational
- Medical or psychological impediment to probable compliance with the protocol.
- Patients with prior history of another malignancy within the last 5 years (excluding
basal cell carcinoma, carcinoma in situ of the cervix, non-melanoma skin cancer, or
controlled superficial bladder cancer).
- Presence of an active acute or chronic infection, including symptomatic urinary tract
infection, HIV (as determined by ELISA and confirmed by Western Blot), viral
hepatitis (as determined by HBsAg and Hepatitis C serology) and surgical site
infection following nephrectomy. Any postoperative complication rendering
experimental therapy unduly hazardous i.e. deep venous thrombosis (DVT) or pulmonary
embolism will exclude eligibility from study.
- Patients on steroid therapy (or other immunosuppressive agents such as azathioprine
or cyclosporine A) are excluded on the basis of potential immune suppression.
Patients must have had 6 weeks of discontinuation of any steroid therapy prior to
- Patients with serum calcium >12 mg/dl or symptomatic hypercalcemia. Documented active
treatment for hypercalcemia is allowed.
- Patients with inadequate peripheral vein access to perform leukapheresis.