Clinical trial NCT05623748: Establishment and Application of 3-Dimensional (3-D) Cell Culture Model of Clinical Circulating Tumor Cells (CTCs)
Official title: Establishment and Application of 3-Dimensional (3-D) Cell Culture Model of Clinical Circulating Tumor Cells (CTCs)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cell Carcinoma
Keywords: CTCs
3-D Cell culture
Cell purification
Cell proliferation
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2022-11-21
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: cancer patients with transitional cell carcinoma

Brief summary: The goal of this observational study is to validate and evaluate the clinical feasibility of using a 3-D cell culture model for CTCs isolation/purification and their cell number expansion in cancer patient with transitional cell carcinoma and patient without cancer.

This project first aims to study the clinical feasibility of utilizing a 3-D cell culture model for the isolation/purification of all possible CTCs in a blood sample in a label-free, viable, and high-purity manner. Through 3-D CTC culture, moreover, the cell number of CTCs can be adequately expanded. All these advantageous features are beyond what is currently possible by using the existing methods. In addition, the harvest of CTCs with above features is found valuable for the subsequent academic researches or clinical studies (e.g. molecular mechanisms underlying cancer metastasis, cancer-related gene mutation, biomarker discovery, and particularly CTCs-based chemotherapy drug testing). These could both facilitate and accelerate scientists to develop new therapeutic solutions for future cancer care.

Detailed description: Circulating tumor cells (CTCs), the rare cell species present in the blood, are considered to mainly contribute to cancer metastasis or relapse. Thus, the detection of CTCs is regarded as an essential clinical tool to detect metastatic cancer. Moreover, CTCs can be the therapeutic target of metastatic cancer care. Therefore, the use of viable CTCs as a biopsy to select therapeutic regimens (e.g. CTCs-based anti-cancer drug testing) opens up a promising route to realize personalized cancer therapy. With the recent advances in cell isolation or detection techniques, various novel approaches have been actively proposed to isolate/detect CTCs. Nevertheless, most of current methods might not be able to obtain the all possible, viable, and label-free CTCs with adequate cell purity and cell number for the subsequent CTCs-based anti-cancer drug testing or other bioassays. To tackle the above technical hurdles, the research project proposes the use of a specific 3-D cell culture technique for the isolation/purification, and cell number expansion of CTCs.

The working principle is based on our preliminary findings showing that the human leukocytes will die away in 3-D cell culture condition, whereas the CTCs will tend to aggregate and proliferate in such environment. Based on this phenomenon, the 3-D CTC cell culture can be used to isolate and purify the viable CTCs from the leukocyte background in a negative selection, and label-free manner, enabling the harvest of the all possible CTCs in a blood sample. Furthermore, the proliferation of CTCs in such 3-D cell culture can adequately expand the cell number of CTCs for the subsequent applications, which is currently impossible using the existing methods.

In the 1st year research project, investigators will further validate and evaluate the clinical feasibility of using a 3-D cell culture model for CTCs isolation/purification and their cell number expansion. In the 2nd and 3rd year research project, investigators will optimize the 3-D cell culture model so as to increase the performances of CTC isolation/purification and proliferation. In the optimization process, investigators will explore the effect of cell culture model (e.g. static or perfusion cell culture, and 3-D cell culture using different 3-D scaffolding materials) or biochemical factors (e.g. glucose concentration, serum concentration, pH, or the supplements of growth factors/cytokines) on the the performances of CTC solation/purification and proliferation. As a whole, investigators hope the proposed research project can find out an efficient and effective approach to isolate/purify/expand clinical CTCs in a viable, label-free, and high-purity manner. These harvested CTCs are valuable for the subsequent analytical tasks.

Eligibility criteria: Inclusion Criteria:

1. patients who agreed with the content of informed consent of the study protocol
2. patients who agreed the researcher to review the medical record
3. adults \>20 years old
4. Patients have the right to asked withdrawing from the trial at any timepoints
5. meet the following requirements (1)cancer participants:cancer patients with transitional cell carcinoma (2)healthy participants:participants without cancer

Exclusion Criteria:

1. Patients who refused the collection of blood and the reviewing of medical record
2. The investigators suggest to withdraw

Primary outcomes:
measure: the effect of cell culture model for the Cell viability
timeFrame: baseline
measure: the effect of cell culture model for the Cell viability
timeFrame: 3 month
measure: the effect of cell culture model for the Cell viability
timeFrame: 6 month
measure: the effect of cell culture model for the Cell number
timeFrame: baseline
measure: the effect of cell culture model for the Cell number
timeFrame: 3 month
measure: the effect of cell culture model for the Cell number
timeFrame: 6 month
Secondary outcomes:
measure: the effect of biochemical factors for glucose concentration
timeFrame: baseline, pre-intervention
measure: the effect of biochemical factors for glucose concentration
timeFrame: 3 month
measure: the effect of biochemical factors for glucose concentration
timeFrame: 6 month
measure: the effect of biochemical factors for the serum concentration of growth factors/cytokines
timeFrame: baseline, pre-intervention
measure: the effect of biochemical factors for the serum concentration of growth factors/cytokines
timeFrame: 3 month
measure: the effect of biochemical factors for the serum concentration of growth factors/cytokines
timeFrame: 6 month
measure: the effect of biochemical factors for the serum pH
timeFrame: baseline
measure: the effect of biochemical factors for the serum pH
timeFrame: 3 month
measure: the effect of biochemical factors for the serum pH
timeFrame: 6 month
Other outcomes:
Locations:
city: New Taipei City
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Ye,Siou-Ru
name: Hsuan-Chih Kuo
role: STUDY_DIRECTOR
References:
citation: Oppenheimer SB. Cellular basis of cancer metastasis: A review of fundamentals and new advances. Acta Histochem. 2006;108(5):327-34. doi: 10.1016/j.acthis.2006.03.008. Epub 2006 May 26.
citation: Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer. 2006 Jun;6(6):449-58. doi: 10.1038/nrc1886.
citation: Konstantopoulos K, Thomas SN. Cancer cells in transit: the vascular interactions of tumor cells. Annu Rev Biomed Eng. 2009;11:177-202. doi: 10.1146/annurev-bioeng-061008-124949.