KK-LC-1 TCR Gene Therapy for Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
Background:Researchers have found a new way to treat cancer using T cell therapy. The therapy used in this study is T Cell Receptor (TCR) Gene Therapy Targeting KK-LC-1, a cancer germline antigen that is expressed by certain cancers. This therapy is a type of treatment in which a participant s T cells (a type of immune system white blood cell) are changed in the laboratory to attack cancer cells and given back to the participant. This treatment might help people with KK-LC-1 positive cancers which may include gastric, breast, cervical, lung and other epithelial Cancers. Epithelial cancers are cancers that begin in the cells that line an organ.Objective:The purpose of this study is to determine the safety of different doses of KK-LC-1 TCR T cells plus aldesleukin to treat metastatic or refractory/recurrent KK-LC-1 positive cancers.Eligibility:Adults aged 18 and older with metastatic or refractory/recurrent KK-LC-1 positive epithelial cancer.Design:Participants will be screened with HLA typing (a blood test needed for eligibility) and KK-LC-1 testing of the cancer tumor (to determine if the cancer is KK-LC-1 positive). A new biopsy may be needed if tumor from an outside location is not available for KK-LC-1 testing. Eligible participants will come to the NIH campus to have a screening evaluation which will include physical exam, review of medical history and current medications, blood and heart tests, imaging (X-ray, CT scan, MRI or PET scan), and evaluation of participant s veins that are used for drawing blood.If the participant is eligible for the study based on the screening evaluation, they will have a baseline evaluation prior to receiving the experimental treatment which may include additional laboratory or imaging tests.Participants will have a large IV catheter inserted into a vein to undergo a procedure called leukapheresis. Leukapheresis is the removal of the blood by a machine to collect specific white blood cells. The remaining blood is returned to the body. This procedure is needed to collect the cells that will be modified to target the cancer. The cells are grown in the lab and given back to the participant through an injection into the participant's tumor. It takes 11-15 days to grow the cells.While the cells are growing, the participant will be admitted to the hospital about one weekbefore the cell infusion to receive 2 types of chemotherapy through an IV catheter over 5 days. The main purpose of the chemotherapy is to make the cells more effective in fighting the cancer tumors. The cells will be given 1-2 days after the last dose of chemotherapy. Within 24 hours after the cell infusion, participants will be given a cell growth factor called aldesleukin through an IV for up to 4 days. Aldesleukin is thought to help the cells live longer in the participant s body. Participants will recover in the hospital until they are well enough to go home, which is usually about 7-12 days after the cell infusion or last dose of aldesleukin.Participants will have a follow-up visit at approximately 40 days after the date of cell infusion. This visit will be to evaluate the safety of the cell therapy and the response of the cancer to the treatment which will include physical examination, lab tests, and imaging studies. If a participant has stable disease or their cancer has responded to the treatment, they will be seen again at 12 weeks post cell infusion, every 3 months x 3 visits, and then every 6 months x 5 years. If a participant s cancer progresses after this therapy, they will be return to their home doctor for further management.After receiving cell therapy, participants will be followed on a long-term gene therapy protocol. Participants will have blood drawn periodically to test if the cells have grown or changed. These blood tests will take place immediately before the cells, and then at 3, 6, and 12 months for the first year and possibly annually thereafter based on the results. These tests can be drawn locally and sent to the NIH. After a participant is off the study, they will be contacted by telephone or mailed questionnaire for a total of 15 years after cell therapy....
Do I need to stop my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, more than four weeks must have passed since any prior systemic therapy before receiving the KK-LC-1 TCR T cells. Participants on active systemic immunosuppressive therapy that cannot be safely withheld are excluded from the trial.
What safety data is available for KK-LC-1 TCR gene therapy for cancer?
The safety data for KK-LC-1 TCR gene therapy includes preclinical studies showing no tumorigenic or mutagenic activity in vitro, no acute toxicity or immunotoxicity in vivo, and no pathological changes in organs due to T cell accumulation. Cross-reactivity studies did not demonstrate cross-reactivity against other human proteins, and CT83 gene expression was restricted to germ cells, with expression noted in various epithelial cancers. These findings support further investigation and clinical testing of KK-LC-1 TCR-Ts for cancer treatment.12345
Is the KK-LC-1 TCR treatment a promising treatment for cancer?
What data supports the idea that KK-LC-1 TCR Gene Therapy for Cancer is an effective treatment?
The available research shows that T-cell receptor (TCR) gene therapy, which includes KK-LC-1 TCR Gene Therapy, has shown promising results in treating certain cancers. For example, TCR gene therapy has been effective in reducing tumor size in some patients and has demonstrated strong antitumor effects in both laboratory and human studies. Additionally, TCR gene therapy can be more effective when combined with specific chemotherapy treatments, although these can have significant side effects. Overall, the research suggests that KK-LC-1 TCR Gene Therapy can be a powerful tool in fighting cancer, especially when other treatments are not effective.69111213
Who Is on the Research Team?
Scott M Norberg, D.O.
Principal Investigator
National Cancer Institute (NCI)
Are You a Good Fit for This Trial?
Adults over 18 with certain advanced KK-LC-1 positive epithelial cancers (like gastric, breast, cervical, lung) that have spread or are unresponsive to treatment. They must have normal organ function and no severe allergies to the trial drugs. Participants can't be on immunosuppressive therapy, have a compromised immune system or serious heart conditions.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Baseline Evaluation
Baseline evaluation including additional laboratory or imaging tests prior to treatment
Leukapheresis and Cell Growth
Leukapheresis procedure to collect T cells, followed by cell growth in the lab for 11-15 days
Chemotherapy
Participants receive chemotherapy to prepare for T cell infusion
T Cell Infusion and Aldesleukin Administration
Infusion of KK-LC-1 TCR T cells followed by aldesleukin administration for up to 4 days
Initial Recovery
Participants recover in the hospital until well enough to go home, usually 7-12 days post-infusion
Follow-up
Participants are monitored for safety and effectiveness after treatment, with visits at 40 days, 12 weeks, every 3 months for 3 visits, then every 6 months for 5 years
Long-term Follow-up
Participants are followed on a long-term gene therapy protocol with periodic blood tests and annual follow-ups for up to 15 years
What Are the Treatments Tested in This Trial?
Interventions
- Aldesleukin
- Cyclophosphamide
- Fludarabine
- KK-LC-1 TCR
KK-LC-1 TCR is already approved in United States for the following indications:
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)
Lead Sponsor