Clinical trial NCT02176746: A Phase I/II Study of Active Immunotherapy With Cancer Stem Cells Vaccine for Colorectal Cancer
Official title: Study of Cancer Stem Cell Vaccine That as a Specific Antigen in Metastatic Adenocarcinoma of the Colorectal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neoplasms,Colorectal
Lead sponsor: Fuda Cancer Hospital, Guangzhou
Sponsor class: OTHER
Collaborators: name: University of Michigan
First posted: 2014-06-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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 colorectal cancer. The investigators will purify T, B cells and generate DCs from the PBMCs of the colorectal cancer patient.On the other hand, investigators will isolate ALDHhigh and ALDHlow tumor cells from the tumor specimen of the colorectal cancer patient using a similar protocol as investigators reported .

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

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

Eligibility criteria: Inclusion Criteria:

1. Age:18 and over
2. Performance status:Karnofsky 70-100%
3. Life expectancy:Greater than 6 months
4. Hematopoietic:Absolute neutrophil count at least 1000/mm 3,Hemoglobin at least 9 g/dL,Platelet count at least 100,000/mm\^3
5. Hepatic:Bilirubin less than 2.0 mg/dL No chronic or acute hepatic disease Renal:Creatinine less than 2.5 mg/dL
6. Cardiovascular:

   No chronic or acute cardiac disease (New York Heart Association class III or IV)
7. Pulmonary:

No chronic or acute pulmonary illness such as asthma or chronic obstructive pulmonary disease

Exclusion Criteria:

1. Patients receiving anticoagulation therapy.
2. Patients receiving any other investigational agents.
3. Patients who test positive for Hepatitis B virus, Hepatitis C virus or HIV. 4、level 3 hypertension; 5、severe coronary disease; 6、 myelosuppression; 7、 respiratory disease; 8、 brain metastasis; 9、 chronic infections

Primary outcomes:
measure: The number of participants with adverse events
timeFrame: up to 3 months
Secondary outcomes:
measure: The secondary objectives are to evaluate vaccine immune responses to the immunizations by the data of body measurements
timeFrame: 1 month
Other outcomes:
measure: The dose of CSC vaccine
timeFrame: up to 3 months
Locations:
city: Guangzhou
country: China
facility: Biological treatment center in Fuda cancer hospital
state: Guangdong
Study officials:
References:
citation: 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):1853-64. doi: 10.1158/0008-5472.CAN-11-1400.