Description:
Cytokine-induced killer (CIK) cells exhibit high proliferation rate and cytotoxic activity in
vitro. The major effector cells are the CD3+CD56+ subset. The cytolytic activity of CIK cells
being independent of MHC restriction implies feasibility in using CIK cells allogeneic to the
tumors. Experiments to block the MHC class-I and -II pathways on tumors-RNA transfected DCs
showed that only MHC class-I blocking led to a significant reduction of heterogeneous CIK
cells cytotoxicity after the co-culture. The safety of CIK cells was demonstrated by the lack
of cytotoxicity toward autologous as well as allogeneic normal cells. Co-culture of CIK cells
with dendritic cells (DCs) has been reported by us and others in a myriad of cancer (e.g.,
cholangiocarcinoma, osteosarcoma, glioblastoma multiforme, multiple myeloma, hepatocellular
carcinoma, pancreatic carcinoma, renal & colon carcinoma, murine leukemia & lymphoma showing
enhancement of anti-tumor cytotoxicity of CIK cell in all. The co-culture of CIK cells with
DCs were reported to decrease the number of professional regulatory/ suppressor T cells
(Treg, CD4+CD25+ cells) and decrease the secretion of IL-10, an immune suppressor cytokine,
whereas the cytotoxic activity against target cells increased.
We have recently brought CIK cells through the preclinical phase (animal study) of human
cholangiocarcinoma treatment. Cholangiocarcinoma (CCA), is a bile duct epithelial cancer
endemic in the Northeast of Thailand, with an increasing incidence discernible in Europe and
North America. Conventional treatments including surgery, chemotherapy, and radiation do not
bring satisfactory survival due to anatomic location, presence of metastases, and high
recurrent rates. These unsatisfactory outcomes urge to search innovative treatments such as
immunotherapy. We reported the safety and efficacy of CIK cells in SCID mice model for
cholangiocarcinoma. Several conditions of human CIK cells were examined using ex vivo
cytotoxic assay and SCID mice pre-inoculated with human cholangiocarcinoma cells. We
monitored the ex vivo cytotoxicity, tumor sizes and immunohistochemistry. Optimal tumor
suppression was observed when CIK cells were pre-exposed to dendritic cells (DCs).
Tumor-infiltrating human CD3+ cells were observed from day 2 - 14, but not in normal tissues
elsewhere. These altogether indicated the specific homing of CIK cells to tumor mass. All
animals did not exhibit any noticeable adverse reaction from the CIK treatments. The
CD3+CD56+ cells are logical candidates for clinical trial while the DC-co-cultured CIK cells
produced similar efficacy and more feasible for clinical application.
With a complete array of in vitro and in vivo study, the next rational step is moving forward
to phase I/II clinical trials for a number of specified solid tumors (i.e.,
cholangiocarcinoma, osteosarcoma, and glioblastoma multiforme, nueroblastoma) using the
optimized autologous CIK cells. Subjects without prior exposure to or weaned for at least 3
months from chemotherapy can be recruited to maintain the integrity of their immunological
system, a critical factor for a successful immunotherapy.
Title
- Brief Title: The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous Cytokine-induced Killer Cells
- Official Title: Phase 1 Study of The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous Cytokine-induced Killer Cells.
Clinical Trial IDs
- ORG STUDY ID:
215-3-2552
- NCT ID:
NCT01868490
- NCT ALIAS:
NCT01573455
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| cytokine induced killer cells | | drug |
Purpose
Cytokine-induced killer (CIK) cells exhibit high proliferation rate and cytotoxic activity in
vitro. The major effector cells are the CD3+CD56+ subset. The cytolytic activity of CIK cells
being independent of MHC restriction implies feasibility in using CIK cells allogeneic to the
tumors. Experiments to block the MHC class-I and -II pathways on tumors-RNA transfected DCs
showed that only MHC class-I blocking led to a significant reduction of heterogeneous CIK
cells cytotoxicity after the co-culture. The safety of CIK cells was demonstrated by the lack
of cytotoxicity toward autologous as well as allogeneic normal cells. Co-culture of CIK cells
with dendritic cells (DCs) has been reported by us and others in a myriad of cancer (e.g.,
cholangiocarcinoma, osteosarcoma, glioblastoma multiforme, multiple myeloma, hepatocellular
carcinoma, pancreatic carcinoma, renal & colon carcinoma, murine leukemia & lymphoma showing
enhancement of anti-tumor cytotoxicity of CIK cell in all. The co-culture of CIK cells with
DCs were reported to decrease the number of professional regulatory/ suppressor T cells
(Treg, CD4+CD25+ cells) and decrease the secretion of IL-10, an immune suppressor cytokine,
whereas the cytotoxic activity against target cells increased.
We have recently brought CIK cells through the preclinical phase (animal study) of human
cholangiocarcinoma treatment. Cholangiocarcinoma (CCA), is a bile duct epithelial cancer
endemic in the Northeast of Thailand, with an increasing incidence discernible in Europe and
North America. Conventional treatments including surgery, chemotherapy, and radiation do not
bring satisfactory survival due to anatomic location, presence of metastases, and high
recurrent rates. These unsatisfactory outcomes urge to search innovative treatments such as
immunotherapy. We reported the safety and efficacy of CIK cells in SCID mice model for
cholangiocarcinoma. Several conditions of human CIK cells were examined using ex vivo
cytotoxic assay and SCID mice pre-inoculated with human cholangiocarcinoma cells. We
monitored the ex vivo cytotoxicity, tumor sizes and immunohistochemistry. Optimal tumor
suppression was observed when CIK cells were pre-exposed to dendritic cells (DCs).
Tumor-infiltrating human CD3+ cells were observed from day 2 - 14, but not in normal tissues
elsewhere. These altogether indicated the specific homing of CIK cells to tumor mass. All
animals did not exhibit any noticeable adverse reaction from the CIK treatments. The
CD3+CD56+ cells are logical candidates for clinical trial while the DC-co-cultured CIK cells
produced similar efficacy and more feasible for clinical application.
With a complete array of in vitro and in vivo study, the next rational step is moving forward
to phase I/II clinical trials for a number of specified solid tumors (i.e.,
cholangiocarcinoma, osteosarcoma, and glioblastoma multiforme, nueroblastoma) using the
optimized autologous CIK cells. Subjects without prior exposure to or weaned for at least 3
months from chemotherapy can be recruited to maintain the integrity of their immunological
system, a critical factor for a successful immunotherapy.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| drug | Experimental | single-group studies | - cytokine induced killer cells
|
Eligibility Criteria
Inclusion Criteria:
1. Patient must be at least 18 year-old, or allowance from their parent if younger than
that.
2. Patient must have histologically or cytologically confirmed advanced
Cholangiocarcinoma by oncologist
3. Cholangiocarcinoma have been failing to current treatment.
4. Patient is healthy by getting an Eastern Co-operative Oncology Group (ECOG)
performances status of 0, 1 or 2.
5. Any of the following lab data
a. Hematology:
- Hb > 8 g/dl
- Absolute neutrophil count (ANC) > 1,500 cells/mm3
- Absolute lymphocyte count > 1,000 cells/mm3
- Platelet > 100x109/L
6. Patient must have a life expectancy of at least 12 weeks by
a. Biochemistry:
- Serum total bilirubin < 3 mg/dl
- Serum creatinine < 2 mg/dl
7. Patients will to comply and provide written informed consent prior to enrollment into
the study.
Exclusion Criteria:
1. Patients received chemotherapy within 4 weeks before study entry.
2. Active uncontrolled infection
3. Concurrent anti-cancer treatment in another investigational trial, including
immunotherapy in last 30 days
4. Pregnant or lactating woman, or women of child bearing potential or less than one year
after menopause (unless surgically sterile) with urine pregnancy test positive
5. Concurrent steroid therapy
| Maximum Eligible Age: | 60 Years |
| Minimum Eligible Age: | 8 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | MRI scan for monitoring of tumor size and CIK cell-homing, Fluorescence-activated cell sorting (FACS) analysis |
| Time Frame: | 6 weeks |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Survival rate |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Siriraj Hospital |
Trial Keywords
- Cholangiocarcinoma
- Cytokine induced killer cells
- CIK
- Treg
- Th17
Last Updated
November 1, 2019
