Pancreatic CancerNCT04203459
The Mechanism of Enhancing the Anti-tumor Effects of CAR-T on PC by Gut Microbiota Regulation
An observational study of Pancreatic Cancer and Gut Microbiota, run by First Affiliated Hospital of Harbin Medical University at 1 site in China.
Trial summary
Pancreatic cancer (PC) is one of the deadliest diseases of human digestive malignancies. Despite the recent advances in surgery and chemotherapy, the 5-year survival rate of PC continues to be less than 10%. Read more about this study
- Who is it for?
- Ages 30 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Pancreatic Cancer, Gut Microbiota, CAR-T
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 20 Oct 2019to 31 Dec 2022
- How long will I take part?
- 6 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Pancreatic cancer patients and Healthy person.
Who may be able to join
- the patients who are confirmed by imaging, pathology and body fluid biopsy to have metastasized pancreatic cancer and can not be cured by operation; or the patients who recover well one month after operation but still have residual focus, recurrence or metastasis.
- age ≥ 30 and ≤ 75
- the estimated life span is more than 1 month.
- Karnofsky score ≥ 60; ECoG ≤ 2
- the function of important organs: Echocardiography indicated that the ejection fraction of heart was ≥ 50%; ECG showed no obvious abnormality; creatinine clearance rate calculated by Cockcroft Gault formula was ≥ 40ml / min; ALT and AST were ≤ 3 times of normal value; total bilirubin was ≤ 2.0mg/dl; coagulation function: Pt and appt were < 2 times of normal value; arterial oxygen saturation (SpO2) > 92%;Blood routine test: Hgb ≥ 80g / L, ANC ≥ 1 × 109 / L, PLT ≥ 50 × 109 / L.
- sign the informed consent.
Who cannot join
- patients who used immunosuppressive drugs, hormones, antibiotics and probiotics one month before admission.
- serious active infection.
- HIV positive, active hepatitis infection.
- previous history of other malignant tumors. Excluding: Patients with cured skin basal or squamous cell carcinoma and cervical carcinoma in situ at any time before the study; patients with other tumors not listed above but cured by operation only without other further treatment measures and disease-free survival period ≥ 5 years can be included in the study.
- patients participating in other clinical trials at the same time. (7) in the opinion of the researcher, the subjects are not suitable to be selected or cannot cooperate to participate in or complete the study.
- patients with congenital immunodeficiency. Exclusion criteria
Show all 15Show fewer
- patients who had used immunosuppressive drugs, hormones, antibiotics and probiotics in the first month before inclusion.
- severe active infection.
- human immunodeficiency virus (HIV) positive, active hepatitis infection.
- previous history of other malignant tumors. Excluding: patients with cured basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix at any time prior to the study; Subjects with disease-free survival ≥5 years of other tumors not listed above, which have been cured by surgery only without other further treatment measures, can be included in the study.
- patients who also participate in other clinical trials. (7) the investigator considers that the subject is not suitable for inclusion or unable to cooperate in or complete the study.
- patients with congenital immune deficiency. (9) a history of myocardial infarction and severe arrhythmia within six months. 2. Inclusion criteria and exclusion criteria for the control group of this project
- no history of digestive tract diseases, infectious diseases or immune diseases.
- no history of smoking or drinking.
- did not take antibiotics and other drugs and probiotics for 1 month before enrollment.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The first affiliated hospital of Harbin medical university
Harbin, Heilongjiang, 150081
Lei Zhao, +860451-85553099, zhaoleihyd@163.com
About this study
Official title: Study on the Mechanism of Enhancing the Anti-tumor Effects of Human Chimeric Antigen Receptors T Cells on Pancreatic Cancer by Gut Microbiota Regulation
Pancreatic cancer (PC) is one of the deadliest diseases of human digestive malignancies. Despite the recent advances in surgery and chemotherapy, the 5-year survival rate of PC continues to be less than 10%. As a promising tumor therapy,Chimeric antigen receptor T cell (CAR-T), however, performed poorly in PC treatment and need to be further updated. In our study, on the basis of our previous research, we use anti-MSLN CAR-T as effector cell and explore the different effects and mechanism of gut microbiota (PC or healthy control) on anti-MSLN CAR-T treatment. Firstly, we detect the differences of gut microbiota and T cell cholesterol metabolism in PC and healthy control by means of 16S-rRNA,PCR, western blot and ELISA; explore the different effects of gut microbiota on the subtype of T cells; and analyze the relationships between intestinal flora composition and T cell cholesterol metabolism or subtype changes by means of Spearman's correlation. Secondly, we also explore the different effects of gut microbiota on the proliferation, migration, subtype, inflammatory cytokines expression and anti-tumor effector function of anti-MSLN CAR-T cells by means of flow cytometry and cytotoxicity assay. Thirdly, we discuss the different expression of cholesterol esterification enzyme 1 (ACAT-1) and other core genes of cholesterol metabolism in anti-MSLN CAR-T. Lastly, we evaluate the effects of different gut microbiota on the treatment of PC by anti-MSLN CAR-T cells in NSG mouse model of subcutaneous PC transplantation and liver metastasis. Through the above experiments, a new theoretical basis is provided in which gut microbiota regulates the subtype and anti-tumor function of anti-MSLN CAR-T by ACAT-1 expression. Furthermore, our findings, which demonstrate the relationship of gut microbiota and CAR-T cell, may be translatable for the treatment of other solid tumors like PC.
- Conditions
- Pancreatic Cancer, Gut Microbiota, CAR-T
- Keywords
- pancreatic cancer, chimeric antigen receptor T cell, gut microbiota, Acyl-CoA, cholesterol acyltransferase 1, Mesothelin
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pancreatic cancer patient | (1) patients with pancreatic cancer confirmed by imaging, pathology and body fluid biopsy, or patients who recovered well one month after operation but still had residual lesions, recurrence or metastasis. ② age ≥ 30 and ≤ 75. ③ no chemotherapy, radiotherapy or targeted drugs were used before admission. ④ patients who had used immunosuppressive drugs, hormones, antibiotics and probiotics one month before admission were excluded. ⑤ patients with HIV positive and active hepatitis B or C infection were excluded. ⑥ exclude the previous history of other malignant tumors or the current combination of other malignant tumors. The patients with serious cardiopulmonary disease and liver and kidney dysfunction were excluded. ⑧ patients with obstructive jaundice were excluded. | |
| Healthy person | (1) no history of digestive tract diseases, infectious diseases or immune diseases.(2) no history of smoking or drinking.(3) did not take antibiotics and other drugs and probiotics for 1 month before enrollment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
In vivo experiment: comparison of intestinal microflora and T cell cholesterol metabolism and subtypes between pancreatic cancer patients and healthy people The difference of proportion and the correlation.
Fecal and peripheral blood samples were collected from patients with pancreatic cancer and healthy people respectively: (1) through Illumina miseq
High throughput sequencing technology was used to detect 16S rRNA to analyze the diversity of intestinal flora (α and β diversity), and bioinformatics methods such as random forest and lefse were used to analyze the diversity of flora composition; (2) the difference of cholesterol content in T cells was detected by ELISA; (3) the difference of ACAT-1 expression in T cells was detected by PCR and WB; (4) the difference of ACAT-1 expression in T cells was detected by flow cytometry. The proportion of CD8 +, TNF α +, Th1, Th2, Th17, Treg and other subtypes in T cells was detected by cell analyzer. Furthermore, the correlation between intestinal microflora composition and peripheral blood T cell cholesterol metabolism and subtype difference was determined by Spearman correlation analysis (statistical method).
Measured: from January 2020 to December 2020.
In vitro experiment: to verify the regulation of intestinal flora on the biological behavior of anti msln car-t in vitro and the role of ACAT-1 in it.
In vitro, intestinal flora supernatant of pancreatic cancer and healthy human were co-cultured with anti-msln car-t, respectively, to verify the effect of intestinal flora on biological behavior of anti-msln car-t.To analyze how the metabolism of cholesterol in anti-msln car-t cells, with acat-1 as the key enzyme, participates in the process of regulating the biological behavior of anti-msln car-t by intestinal flora, and preliminarily uncover the relevant mechanism.
Measured: from January 2021 to December 2021.
Animal model experiment: to verify the ability of intestinal bacteria to control anti msln car-t targeted killing pancreatic cancer cells.
Furthermore, the influence of differences in intestinal flora composition between pancreatic cancer and healthy human on anti-msln car-t function was verified in animal models of pancreatic cancer.
Measured: from January 2022 to December 2022.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2019
- Study start20 Oct 2019
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
- Target duration
- 6 Months
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Harbin Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04203459
- Sponsor's protocol ID
- Yunwei Wei 2019-10-20
- Status last verified
- Oct 2019
- First submitted
- 16 Dec 2019
- Last updated
- 18 Dec 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Personal privacy involved
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on the Mechanism of Enhancing the Anti-tumor Effects of Human Chimeric Antigen Receptors T Cells on Pancreatic Cancer by Gut Microbiota Regulation
- ClinicalTrials.gov ID
- NCT04203459
- Acronym / sponsor ID
- Yunwei Wei 2019-10-20
- Conditions
- Pancreatic Cancer, Gut Microbiota, CAR-T
- Keywords
- pancreatic cancer, chimeric antigen receptor T cell, gut microbiota, Acyl-CoA, cholesterol acyltransferase 1, Mesothelin
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Harbin Medical UniversityUniversity, hospital or other
- Study start
- 20 Oct 2019 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 18 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pancreatic cancer (PC) is one of the deadliest diseases of human digestive malignancies. Despite the recent advances in surgery and chemotherapy, the 5-year survival rate of PC continues to be less than 10%. As a promising tumor therapy,Chimeric antigen receptor T cell (CAR-T), however, performed poorly in PC treatment and need to be further updated. In our study, on the basis of our previous research, we use anti-MSLN CAR-T as effector cell and explore the different effects and mechanism of gut microbiota (PC or healthy control) on anti-MSLN CAR-T treatment. Firstly, we detect the differences of gut microbiota and T cell cholesterol metabolism in PC and healthy control by means of 16S-rRNA,PCR, western blot and ELISA; explore the different effects of gut microbiota on the subtype of T cells; and analyze the relationships between intestinal flora composition and T cell cholesterol metabolism or subtype changes by means of Spearman's correlation. Secondly, we also explore the different effects of gut microbiota on the proliferation, migration, subtype, inflammatory cytokines expression and anti-tumor effector function of anti-MSLN CAR-T cells by means of flow cytometry and cytotoxicity assay. Thirdly, we discuss the different expression of cholesterol esterification enzyme 1 (ACAT-1) and other core genes of cholesterol metabolism in anti-MSLN CAR-T. Lastly, we evaluate the effects of different gut microbiota on the treatment of PC by anti-MSLN CAR-T cells in NSG mouse model of subcutaneous PC transplantation and liver metastasis. Through the above experiments, a new theoretical basis is provided in which gut microbiota regulates the subtype and anti-tumor function of anti-MSLN CAR-T by ACAT-1 expression. Furthermore, our findings, which demonstrate the relationship of gut microbiota and CAR-T cell, may be translatable for the treatment of other solid tumors like PC.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 6 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pancreatic cancer patient | – | –(1) patients with pancreatic cancer confirmed by imaging, pathology and body fluid biopsy, or patients who recovered well one month after operation but still had residual lesions, recurrence or metastasis. ② age ≥ 30 and ≤ 75. ③ no chemotherapy, radiotherapy or targeted drugs were used before admission. ④ patients who had used immunosuppressive drugs, hormones, antibiotics and probiotics one month before admission were excluded. ⑤ patients with HIV positive and active hepatitis B or C infection were excluded. ⑥ exclude the previous history of other malignant tumors or the current combination of other malignant tumors. The patients with serious cardiopulmonary disease and liver and kidney dysfunction were excluded. ⑧ patients with obstructive jaundice were excluded. |
| Healthy person | – | –(1) no history of digestive tract diseases, infectious diseases or immune diseases.(2) no history of smoking or drinking.(3) did not take antibiotics and other drugs and probiotics for 1 month before enrollment. |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Pancreatic cancer patients and Healthy person.
Key inclusion criteria (6 listed)
- the patients who are confirmed by imaging, pathology and body fluid biopsy to have metastasized pancreatic cancer and can not be cured by operation; or the patients who recover well one month after operation but still have residual focus, recurrence or metastasis.
- age ≥ 30 and ≤ 75
- the estimated life span is more than 1 month.
- Karnofsky score ≥ 60; ECoG ≤ 2
- the function of important organs: Echocardiography indicated that the ejection fraction of heart was ≥ 50%; ECG showed no obvious abnormality; creatinine clearance rate calculated by Cockcroft Gault formula was ≥ 40ml / min; ALT and AST were ≤ 3 times of normal value; total bilirubin was ≤ 2.0mg/dl; coagulation function: Pt and appt were < 2 times of normal value; arterial oxygen saturation (SpO2) > 92%;Blood routine test: Hgb ≥ 80g / L, ANC ≥ 1 × 109 / L, PLT ≥ 50 × 109 / L.
Key exclusion criteria (15 listed)
- patients who used immunosuppressive drugs, hormones, antibiotics and probiotics one month before admission.
- serious active infection.
- HIV positive, active hepatitis infection.
- previous history of other malignant tumors. Excluding: Patients with cured skin basal or squamous cell carcinoma and cervical carcinoma in situ at any time before the study; patients with other tumors not listed above but cured by operation only without other further treatment measures and disease-free survival period ≥ 5 years can be included in the study.
- patients participating in other clinical trials at the same time. (7) in the opinion of the researcher, the subjects are not suitable to be selected or cannot cooperate to participate in or complete the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
In vivo experiment: comparison of intestinal microflora and T cell cholesterol metabolism and subtypes between pancreatic cancer patients and healthy people The difference of proportion and the correlation.
Time frame: from January 2020 to December 2020.
Fecal and peripheral blood samples were collected from patients with pancreatic cancer and healthy people respectively: (1) through Illumina miseq High throughput sequencing technology was used to detect 16S rRNA to analyze the diversity of intestinal flora (α and β diversity), and bioinformatics methods such as random forest and lefse were used to analyze the diversity of flora composition; (2) the difference of cholesterol content in T cells was detected by ELISA; (3) the difference of ACAT-1 expression in T cells was detected by PCR and WB; (4) the difference of ACAT-1 expression in T cells was detected by flow cytometry. The proportion of CD8 +, TNF α +, Th1, Th2, Th17, Treg and other subtypes in T cells was detected by cell analyzer. Furthermore, the correlation between intestinal microflora composition and peripheral blood T cell cholesterol metabolism and subtype difference was determined by Spearman correlation analysis (statistical method).
In vitro experiment: to verify the regulation of intestinal flora on the biological behavior of anti msln car-t in vitro and the role of ACAT-1 in it.
Time frame: from January 2021 to December 2021.
In vitro, intestinal flora supernatant of pancreatic cancer and healthy human were co-cultured with anti-msln car-t, respectively, to verify the effect of intestinal flora on biological behavior of anti-msln car-t.To analyze how the metabolism of cholesterol in anti-msln car-t cells, with acat-1 as the key enzyme, participates in the process of regulating the biological behavior of anti-msln car-t by intestinal flora, and preliminarily uncover the relevant mechanism.
Animal model experiment: to verify the ability of intestinal bacteria to control anti msln car-t targeted killing pancreatic cancer cells.
Time frame: from January 2022 to December 2022.
Furthermore, the influence of differences in intestinal flora composition between pancreatic cancer and healthy human on anti-msln car-t function was verified in animal models of pancreatic cancer.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2019.
- Individual participant dataSharing planned: No. Personal privacy involved
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pancreatic Cancer and Gut Microbiota, run by First Affiliated Hospital of Harbin Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yunwei Wei (+860451-85553099, hydwyw11@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In vivo experiment: comparison of intestinal microflora and T cell cholesterol metabolism and subtypes between pancreatic cancer patients and healthy people The difference of proportion and the correlation. (time frame: from January 2020 to December 2020.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2019; AzTrials last refreshed its copy on 8 Nov 2026.