18 Participants Needed

CAR T Cell Immunotherapy for Pancreatic Cancer

AC
MO
Overseen ByMark O'Hara, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or systemic steroids, you may need to stop them at least 4 weeks before joining the trial.

What data supports the effectiveness of the treatment huCART-meso cells for pancreatic cancer?

Research shows that huCART-meso cells, which are engineered to target a protein called mesothelin found in pancreatic tumors, have been effective in animal studies by entering tumors and destroying cancer cells, nearly doubling survival times. In a small human trial, this treatment stabilized the disease in some patients and significantly reduced tumor activity in one patient, suggesting potential antitumor effects.12345

Is CAR T cell immunotherapy safe for humans?

Research shows that CAR T cell therapy targeting mesothelin in pancreatic cancer patients is generally safe, with no severe side effects like cytokine release syndrome (a severe immune reaction) or neurological symptoms reported. In studies, the treatment was well tolerated, and no dose-limiting toxicities (serious side effects that prevent increasing the dose) were observed.14567

How is the CAR T Cell Immunotherapy for Pancreatic Cancer treatment different from other treatments?

This treatment is unique because it uses genetically engineered T cells, called CAR T cells, to specifically target and attack cancer cells that express a protein called mesothelin, which is often found in pancreatic cancer. Unlike traditional treatments, this approach aims to harness the body's immune system to fight the cancer, offering a novel option for a condition with limited effective treatments.148910

What is the purpose of this trial?

Phase I study to establish the safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells in patients with histologically confirmed unresectable or metastatic pancreatic adenocarcinoma

Research Team

MO

Mark O'Hara, MD

Principal Investigator

Assistant Professor of Medicine, Penn Medicine

Eligibility Criteria

This trial is for adults over 18 with advanced pancreatic cancer that can't be surgically removed or has spread, and who have already tried at least one chemotherapy. They must have a certain level of health and organ function, not have other active cancers or infections like HIV or hepatitis, no recent immunosuppressants use, and agree to birth control methods.

Inclusion Criteria

Subjects of reproductive potential must agree to use acceptable birth control methods
I have tried at least one standard chemotherapy for my advanced disease.
My advanced disease has not worsened on first-line chemotherapy.
See 7 more

Exclusion Criteria

I need extra oxygen to help me breathe.
I have had treatment with gene-modified cells before.
History of allergy or hypersensitivity to study product excipients
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of lentiviral transduced huCART-meso cells via different delivery methods depending on cohort assignment

1 day per infusion, with additional infusions possible between 21-42 days apart
Multiple visits for infusions and assessments

Safety Monitoring

Participants are monitored for dose-limiting toxicities (DLTs) and adverse events

21 days post-infusion for initial safety follow-up
Regular visits for safety assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • huCART-meso cells
Trial Overview The study tests the safety of huCART-meso cells delivered either through the veins or directly into the tumor in patients with pancreatic cancer. It's an early-phase trial (Phase I) focusing on whether this method is safe and doable.
Participant Groups
5Treatment groups
Experimental Treatment
Group I: Cohort 4 - huCART meso cells via intrahepatic infusion (hepatic arterial infusion)Experimental Treatment1 Intervention
Subjects will receive a single dose of of 1-3x10\^7 cells/m\^2 lentiviral transduced huCART-meso cells on day 0 following a minimum 1 week washout from standard care chemotherapy. This initial intrahepatic infusion may be followed by up to two additional infusions of huCART-meso cells via intravenous (IV) administration at the same dose level, given between 21-42 days apart.
Group II: Cohort 3 - huCART meso cells via intrahepatic infusion (hepatic arterial infusion)Experimental Treatment1 Intervention
Permanently closed
Group III: Cohort 2 - huCART meso cells via intraperitoneal infusion (IP)Experimental Treatment1 Intervention
Permanently closed
Group IV: Cohort 1: huCART-meso cells via intravenous infusion (IV).Experimental Treatment1 Intervention
Subjects will receive a single dose of 1-3x10\^7/m\^2 lentiviral transduced huCART-meso cells on day 0 via intravenous infusion.
Group V: Cohort -1: low dose huCART-meso cells via intravenous infusionExperimental Treatment1 Intervention
In the event that 2 DLTs occur among subjects enrolled in Cohort 1, then enrollment in Cohort 1 will be stopped and the dose will be de-escalated by 10-fold to 1-3x10\^6 cells/m\^2. Subjects will receive a single dose of 1-3x10\^6 cells/m\^2 lentiviral transduced huCART-meso cells on day 0.

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials
2,118
Recruited
45,270,000+

Findings from Research

Meso-CART cells, engineered T cells targeting mesothelin, showed promising anti-tumor effects against pancreatic cancer, particularly in eliminating lung metastases in mice, indicating potential for treating advanced stages of the disease.
This study is the first to demonstrate that meso-CART cells can effectively target and reduce distant metastases, suggesting they could be a viable immunotherapy option for patients with mesothelin-positive pancreatic tumors.
Engineered T lymphocytes eliminate lung metastases in models of pancreatic cancer.Sun, Q., Zhou, S., Zhao, J., et al.[2019]
Engineered T cells targeting mesothelin, a protein overproduced by pancreatic tumors, effectively infiltrated and destroyed cancer cells in mice.
The treatment significantly improved survival times in the mice, nearly doubling their lifespan, indicating a promising approach for pancreatic cancer therapy.
T Cells Target Pancreatic Tumors.Leslie, M.[2021]
Blocking Interleukin-10 in the tumor microenvironment significantly enhances the effectiveness of mesothelin-chimeric antigen receptor T cell therapy, as it restores the secretion of key cytokines like interferon γ and granzyme B that are essential for killing cancer cells.
In experiments, T cells exposed to pancreatic cancer cell-conditioned medium showed reduced cytotoxicity, but this effect was notably reversed when Interleukin-10 was depleted, suggesting a promising strategy to improve immunotherapy outcomes in pancreatic cancer.
Inhibition of Interleukin-10 in the tumor microenvironment can restore mesothelin chimeric antigen receptor T cell activity in pancreatic cancer in vitro.Batchu, RB., Gruzdyn, OV., Mahmud, EM., et al.[2021]

References

Engineered T lymphocytes eliminate lung metastases in models of pancreatic cancer. [2019]
T Cells Target Pancreatic Tumors. [2021]
Inhibition of Interleukin-10 in the tumor microenvironment can restore mesothelin chimeric antigen receptor T cell activity in pancreatic cancer in vitro. [2021]
Dual Targeting of Mesothelin and CD19 with Chimeric Antigen Receptor-Modified T Cells in Patients with Metastatic Pancreatic Cancer. [2023]
Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastases in a Phase 1 Trial. [2022]
Engineered CAR T cells targeting mesothelin by piggyBac transposon system for the treatment of pancreatic cancer. [2021]
Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancreatic malignancy. [2021]
The Potential of CAR T Cell Therapy in Pancreatic Cancer. [2022]
Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Immunotherapy Shows Promise in Pancreatic Cancer. [2020]
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