HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma

Updated on 22 December 2020
primary cancer
metastatic cancer
clear cell renal cell carcinoma
renal cell cancer
clear cell carcinoma


Gene transfer is a new cancer therapy takes white blood cells from a person and grows them in a lab. The cells are changed with a virus to attack tumor cells, then returned to the person. Researchers want to see if this therapy fights kidney cancer cells.

Metastatic renal cell carcinoma (RCC) is an incurable condition. Current therapy for this disease consists of the serial administration of agents such as VEGF, mTOR inhibitors and immunotherapy (high-dose (HD) IL-2 or immune-checkpoint inhibitors). Long-term survival can be achieved with high-doses IL-2 or immune-checkpoint inhibitors. However, of those patients treated with immunotherapy, three quarters will not respond at all and only 5-8% will achieve a complete and durable response.



Our team isolated a tumor-specific cytotoxic T lymphocyte (CTL) line from peripheral blood mononuclear cells (PBMCs) obtained after an allogeneic transplant from a patient who showed prolonged tumor regression. Using limiting dilution cloning, we identified an allogeneic (derived from the stem cell donor) CD8+ T-cell clone that killed ccRCC cells in an HLA A11 restricted fashion. Using cDNA expression cloning, we identified a HERV-E derived antigen expressed in the patient s ccRCC cells to be the target of this T-cell clone. Remarkably, we found this HERV-E was expressed in the majority of ccRCC cells with no expression in normal tissues. Based on the identification of the antigenicity of the HERV-E transcripts in ccRCC, our team in collaboration with Dr. Nishimura s laboratory (Loyola University Cardinal Bernardin Cancer Center) has cloned, expressed and characterized the TCR from this CD8+ T-cell clone that recognizes an HLA A11 restricted HERV-E antigen.

This research protocol is therefore designed to evaluate the safety and effectiveness of infusion of HERV-E TCR transduced CD8+/CD34+ enriched T cells in HLA-A*11:01 positive patients with metastatic clear cell RCC. Subjects will receive a novel non-myeloablative immunosuppressive conditioning regimen of cyclophosphamide and fludarabine followed by an infusion of HERV-E TCR transduced CD8+/CD34+ enriched T cells. To mediate T cell survival and sustain function, moderate-doses of IL-2 (aldesleukin) will be administered intravenously twice a day for 7 days.

The primary endpoint is safety by day 21. Secondary endpoints will include overall response rate, progressionfree survival and overall survival. We will also evaluate for the persistence of circulating HERV-E TCR transduced CD8+/CD34+ enriched T cells, changes in immune cell subsets and activation status of T cells, as well as, other immunologic determinants with clinical outcomes at baseline, at different time points during treatment and at the time of disease progression.

For more information about this study you can access the NIH patient recruitment study page.


Researchers at the National Institutes of Health (NIH) in Bethesda, Maryland, in partnership with Loyola University Chicago, are enrolling patients with kidney cancer (renal cell carcinoma) into a gene therapy study – a new type of precision medicine that genetically reprograms your immune cells to specifically recognize and kill tumor cells. Immunotherapy has shown to be more effective than the targeted therapies approved for kidney cancer treatment.

T cells are part of the immune system that help protect the body from infection and may help fight cancer. Too often, T cells do not recognize cancer cells or they end up becoming burned-out and lose their fighting ability. The most advanced type of cancer immunotherapy to boost your immune system is gene therapy. It consists of enhancing the T cells from the blood of a patient by genetically reprogramming them in a laboratory. These now “boostered” T cells are given back to the patient allowing the immune system to have clearer directions for recognizing and fighting cancer cells. Dr. Richard Childs’ team discovered that the vast majority of clear-cell kidney cancers have tumor cells that express a protein called HERV-E. When a patient’s immune system recognizes this protein, the immune cells are able to kill the cancer cells. With this new gene therapy, we booster your T cells to recognize HERV-E and destroy your tumor cells. This is an early phase trial looking at whether this gene therapy is safe and benefits patients.

During the Study:

You will undergo leukapheresis, a process to obtain a collection of your immune cells including T cells. We will modify these cells in a laboratory through gene therapy to direct them against your cancer. You will receive chemotherapy through a vein to prepare your immune system for the modified immune cells.

Approximately 5 weeks after the leukapheresis, you will be infused with your own immune cells, re-directed to work better at recognizing your tumor. You will also receive aldesleukin (IL-2) about every 12 hours for up to 14 doses so your enhanced T cells can grow and have a better chance at killing your tumor. You will stay at the Clinical Center, NIH’s research hospital for at least 2 weeks after the re-infusion of the boostered T cells.

You may be eligible if:

  • You are between the ages of 18 and 70
  • You have been diagnosed with kidney cancer type clear cell
  • Your disease is metastatic (has spread)

Doctor referral not required.

Condition Cancer/Tumors, Metastatic Clear Cell Renal Cell Carcinoma Genetically Modified Lymphocytes
Clinical Study IdentifierTX217948
Last Modified on22 December 2020


Yes No Not Sure

Inclusion Criteria

People ages 18-70 years old with a certain type of kidney cancer
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note