45 Participants Needed

AFPᶜ³³²T Cells for Advanced Liver Cancer

Recruiting at 20 trial locations
AB
Overseen ByAnthony B El-Khoueiry, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must stop cytotoxic chemotherapy, immune therapy, and biological therapy 3 weeks before leukapheresis, and corticosteroids or other immunosuppressive therapy 2 weeks before. Specific cancer drugs like Sorafenib must be stopped 1 week before, and Cabozantinib 2 weeks before. Discuss any other medications with the study physician.

What data supports the effectiveness of the treatment AFPᶜ³³²T for advanced liver cancer?

Research shows that targeting alpha-fetoprotein (AFP), a protein often found in high levels in liver cancer, can trigger strong immune responses against cancer cells. Studies using similar approaches have demonstrated that engineered immune cells can effectively attack liver cancer cells by recognizing AFP as a target.12345

Is AFPᶜ³³²T treatment safe for humans?

The safety of AFPᶜ³³²T treatment specifically isn't detailed in the provided research, but similar treatments targeting alpha-fetoprotein (AFP) in liver cancer have shown promising safety profiles. For example, a study on T cell receptors targeting AFP in liver cancer found a candidate with an optimal safety profile, and another study on invariant natural killer T cells for liver cancer reported no severe adverse events.56789

What makes the AFPᶜ³³²T treatment unique for advanced liver cancer?

The AFPᶜ³³²T treatment is unique because it targets alpha-fetoprotein (AFP), a protein often elevated in liver cancer, to potentially enhance the immune system's ability to fight cancer cells. This approach is different from standard treatments as it focuses on using the body's immune response to specifically target cancer cells associated with AFP.510111213

What is the purpose of this trial?

This first time in human study is intended for men and women between 18 and 75 years of age who have advanced liver cancer which has grown or returned after being treated or another AFP expressing tumor. Those who did not tolerate or refused other therapies may also participate. The purpose of this study is to test the safety of genetically changed T cells that target alpha-fetoprotein (AFP) and find out what effects, if any, they have in subjects with liver cancer or other AFP expressing tumor types. This study is for subjects who have a blood test positive for appropriate HLA-A\*02 P Group and have adequate AFP protein in blood or tumor, and whose noncancerous liver tissue has very little AFP protein (Liver only).The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells.The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion after 3 days of chemotherapy. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose.Subjects will be hospitalized for at least 1 week after receiving their T cells back and then seen frequently by the Study Physician for the next 6 months. After that, subjects will be seen every three months. If subjects have disease progression or withdraw from the study, they will then be entered into a long-term follow up for safety monitoring. In long-term follow up, subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion and annually for the next 10 years.

Research Team

RS

Richard S Finn, MD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

This trial is for adults aged 18-75 with advanced liver cancer or other AFP expressing tumors, who have not responded to standard treatments or cannot tolerate them. Participants must have a life expectancy over 4 months, measurable disease progression, and specific levels of alpha-fetoprotein (AFP) in their blood and tumor cells. They should be relatively healthy otherwise, with adequate organ function and no severe heart or psychiatric conditions.

Inclusion Criteria

My organs are functioning well.
My liver cancer can't be treated with surgery or transplant. I may have treatment targeting specific areas after joining.
My cancer has worsened despite treatment, or I cannot tolerate or refuse standard treatments.
See 7 more

Exclusion Criteria

I had major surgery over 4 weeks ago and have recovered from it.
I have a severe autoimmune disease but not autoimmune hepatitis.
I used an experimental vaccine 2 months ago without improvement in my cancer.
See 27 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

T Cell Manufacturing

The subject's T cells are collected and sent to a laboratory to be genetically modified

4 weeks

Chemotherapy

Participants receive 3 days of chemotherapy prior to T cell infusion

1 week

Treatment

Participants receive an intravenous infusion of genetically modified T cells and are hospitalized for at least 1 week

1 week
Hospitalization for at least 1 week

Initial Follow-up

Participants are seen frequently by the Study Physician for monitoring after T cell infusion

6 months
Frequent visits

Extended Follow-up

Participants are seen every three months for continued monitoring

up to 2 years
Every 3 months

Long-term Follow-up

Participants are monitored for safety and effectiveness every 6 months for the first 5 years, then annually for the next 10 years

15 years
Every 6 months for 5 years, then annually

Treatment Details

Interventions

  • AFPᶜ³³²T
Trial Overview The study tests genetically modified T cells targeting the AFP protein on cancer cells. Patients' own T cells are taken and engineered in a lab to fight the cancer, then reinfused after chemotherapy. The trial aims to determine the safest dose level of these modified T cells and observe their effects on liver cancer or other AFP expressing tumors over time.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Autologous genetically modified AFPᶜ³³²T cellsExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Adaptimmune

Lead Sponsor

Trials
25
Recruited
10,000+

Findings from Research

The administration of autologous invariant natural killer T (iNKT) cells in 10 patients with advanced hepatocellular carcinoma was found to be safe and well-tolerated, with no severe adverse events reported, even at high doses (up to 1×10^10 cells).
Expanded iNKT cells showed a strong T-helper 1-like immune response, producing significant amounts of cytokines associated with antitumor activity, suggesting potential effectiveness in treating hepatocellular carcinoma, warranting further research.
Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial.Gao, Y., Guo, J., Bao, X., et al.[2021]
A new T cell receptor (TCR) targeting the alpha-fetoprotein (AFP) peptide has been identified as a promising candidate for immunotherapy against hepatocellular carcinoma (HCC), showing effective anti-tumor activity while minimizing cross-reactivity with normal tissues.
The selected AFP TCR has undergone rigorous testing for safety and efficacy, leading to the initiation of an early phase clinical trial (NCT03971747) to evaluate its effectiveness in treating HCC patients.
Selection of a Clinical Lead TCR Targeting Alpha-Fetoprotein-Positive Liver Cancer Based on a Balance of Risk and Benefit.Luo, X., Cui, H., Cai, L., et al.[2021]

References

[Immunization with dendritic cells infected with human AFP adenovirus vector effectively elicits immunity against mouse hepatocellular carcinomas]. [2006]
2.Russia (Federation)pubmed.ncbi.nlm.nih.gov
[Alpha-fetoprotein immunotherapy as a stage of combined treatment of cancer patients]. [2006]
Alpha-fetoprotein-specific genetic immunotherapy for hepatocellular carcinoma. [2012]
Research Progress in Alpha-fetoprotein-induced Immunosuppression of Liver Cancer. [2022]
Patient-derived dendritic cells transduced with an a-fetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells. [2008]
Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial. [2021]
Induction of alpha-fetoprotein-specific CD4- and CD8-mediated T-cell response using RNA-transfected dendritic cells. [2006]
Artificial antigen-presenting cells expressing AFP(158-166) peptide and interleukin-15 activate AFP-specific cytotoxic T lymphocytes. [2018]
Selection of a Clinical Lead TCR Targeting Alpha-Fetoprotein-Positive Liver Cancer Based on a Balance of Risk and Benefit. [2021]
Alpha-fetoprotein producing cells act as cancer progenitor cells in human cholangiocarcinoma. [2022]
The Clinical Significance of Alpha-Fetoprotein mRNAs in Patients with Hepatocellular Carcinoma. [2020]
The Expressions of CD44, CD90 and Alpha Fetoprotein Biomarkers in Indonesian Patients with Advanced Liver Disease: an Observational Study. [2020]
13.United Statespubmed.ncbi.nlm.nih.gov
Xenotransplantation of alpha-fetoprotein-producing gastric cancers into nude mice. Characteristics and responses to chemotherapy. [2019]
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