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The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous CIK Cells

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	8 Years - 60 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Patient must be at least 8 year-old, or allowance from their parent if younger than that. 2. Patient must have histologically or cytologically confirmed advanced cholangiocarcinoma or neuroblastoma by oncologist. 3. The cancers 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 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT01868490
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Siriraj Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Adisak Wongkajornsilp, M.D., Ph.D.
Principal Investigator Affiliation	Mahidol University
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Enrolling by invitation
Countries	Thailand
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Cholangiocarcinoma, Neuroblastoma

Arms & Interventions

Arms

Experimental: drug

single-group studies

Interventions

Drug: - cytokine induced killer cells

at least 10*9 CIK cells, IV on day 0, 14, 28

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Bangkoknoi, Bangkok, Thailand

Status

Address

Siriraj Clinical Research Center, Siriraj Hospital

Bangkoknoi, Bangkok, 10700

Bangkok, Thailand