A Phase I/II Study of Active Immunotherapy With Cancer Stem Cells Vaccine for Colorectal Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Study of Cancer Stem Cell Vaccine That as a Specific Antigen in Metastatic Adenocarcinoma of the Colorectal

Conditions
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Neoplasms,Colorectal

Intervention / Treatment
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* Biological: cancer stem cell vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age:18 and over Performance status:Karnofsky 70-100% Life expectancy:Greater than 6 months Hematopoietic:Absolute neutrophil count at least 1000/mm 3,Hemoglobin at least 9 g/dL,Platelet count at least 100,000/mm^3 Hepatic:Bilirubin less than 2.0 mg/dL No chronic or acute hepatic disease Renal:Creatinine less than 2.5 mg/dL Cardiovascular: No chronic or acute cardiac disease (New York Heart Association class III or IV) Pulmonary: No chronic or acute pulmonary illness such as asthma or chronic obstructive pulmonary disease Exclusion Criteria: Patients receiving anticoagulation therapy. Patients receiving any other investigational agents. 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

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: non-cancer stem cell vaccine<br>This is no cancer stem cells vaccine in this group | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving low dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving middle dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving high dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of participants with adverse events |  | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objectives are to evaluate vaccine immune responses to the immunizations by the data of body measurements |  | 1 month |