Cancer Stem Cells Vaccine Therapy in Treating Hepatocellular Cancer Patients

Neoplasms, Liver Clinical Trial

Official title:

Study of Cancer Stem Cell Vcccinie That as a Specific Antigen in Metastatic Adenocarcinoma of the Liver

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02089919
• Other study ID #: CLH-001
• Secondary ID: 201401
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 16, 2014
• Last updated: June 1, 2015
• Start date: February 2014
• Est. completion date: February 2015

Study information

• Verified date: March 2014
• Source: Fuda Cancer Hospital, Guangzhou
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Most studies of cancer stem cells (CSC) involve the inoculation of cells from human tumors into immunosuppressed mice, preventing an assessment on the immunologic interactions and effects of CSCs. In this study, the investigators examined the vaccination effects produced by CSC-enriched populations from histologically distinct murine tumors after their inoculation into different syngeneic immunocompetent hosts. Enriched CSCs were immunogenic and more effective as an antigen source than unselected tumor cells in inducing protective antitumor immunity.Immune sera from CSC-vaccinated hosts contained high levels of IgG which bound to CSCs, resulting in CSC lysis in the presence of complement.CTLs generated from peripheral blood mononuclear cells or splenocytes harvested from CSC-vaccinated hosts were capable of killing CSCs in vitro. Mechanistic investigations established that CSC-primed antibodies and T cells were capable of selective targeting CSCs and conferring anti-tumor immunity.

Description:

To assess the feasibility of generating CSC-loaded DC vaccines for clinical use, the investigators will harvest peripheral blood and tumor specimen from patients with hepatocellular cancer. The investigators will purify T, B cells and generate DCs from the PBMCs of the hepatocellular cancer patient.On the other hand, investigators will isolate ALDHhigh and ALDHlow tumor cells from the tumor specimen of the hepatocellular cancer patient using a similar protocol as investigators reported .

Aim 1: To demonstrate, in vitro, the relative cellular anti-hepatocellular cancer CSC immunity induced by hepatocellular cancer CSC-DC primed cytotoxic T cells.

Aim 2: To determine, in vitro, specific binding and lysis of hepatocellular cancer CSCs by antibodies produced by purified B cells from PBMCs stimulated with hepatocellular cancer CSC-DC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Any patients with a diagnosis of HCC based on histology or the current accepted radiological measures.

2. Age > 18 years.

3. Patient has an MRI or CT result (positive for HCC) up to 3 months prior to recruitment.

4. AFP >30.

5. Patient who is not eligible for or failed any HCC treatment.

6. Karnofsky performance status >70%.

7. The patient shows normal organ function according to the following parameters(as measured within six weeks prior to treatment allocation):

Hemoglobin: Within normal range according to institutional standards; Absolute leukocyte count: Within normal range according to institutional standards; Absolute lymphocyte count: Within normal range according to institutional standards; Platelet count: Within normal range according to institutional standards; Alanine aminotransferase: = 2.5 x Upper Limit of Normal (ULN); Aspartate aminotransferase: = 2.5 x ULN; Total bilirubin: = 1.5 x ULN. In the case of known Gilbert's syndrome = 2 x ULN; Serum creatinine: 1.5 x ULN; Calculated creatinine clearance: > 50 mL/min .

8. No history of autoimmune diseases.

9. Ability to understand the study protocol and a willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients receiving anticoagulation therapy.

2. Patients who have received prior gemcitabine or radiation therapy to the liver bed.

3. Patients receiving any other investigational agents.

4. Patients with known brain metastases will be excluded because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse effects.

5. Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.

6. Patients who test positive for Hepatitis B virus, Hepatitis C virus or HIV. 7. level 3 hypertension; 8. severe coronary disease; 9. myelosuppression; 10. respiratory disease; 11. brain metastasis; 12. chronic infections

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Neoplasms
• Neoplasms, Liver

Intervention

Biological:
• cancer stem cell vaccine

Locations

Country	Name	City	State
China	Biological treatment center in Fuda cancer hospital	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Fuda Cancer Hospital, Guangzhou	University of Michigan

Country where clinical trial is conducted

China, 

References & Publications (1)

Ning N, Pan Q, Zheng F, Teitz-Tennenbaum S, Egenti M, Yet J, Li M, Ginestier C, Wicha MS, Moyer JS, Prince ME, Xu Y, Zhang XL, Huang S, Chang AE, Li Q. Cancer stem cell vaccination confers significant antitumor immunity. Cancer Res. 2012 Apr 1;72(7):1853- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The dose of CSC vaccine		up to 3 months	Yes
Primary	The number of participants with adverse events		up to 3 months	Yes
Secondary	The secondary objectives are to evaluate vaccine immune responses to the immunizations by the data of body measurements		1 month	Yes

External Links

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