ACKC Funds Fellow at NIH

ACKC has embarked on an exciting new project to raise money to support the work of Dr. Richard Childs of the National Institutes of Health. Dr. Childs, one of the most renowned kidney cancer researchers in the country, has recently identified a tumor antigen that was derived from a newly discovered gene expressed in 70% of kidney cancer patients. This gene turns out to be a virus, which Dr. Childs hopes will lend itself to the development of an anti-tumor vaccine.

In the autumn of 2006, ACKC embarked upon a project to raise $110,000 to fund a researcher for a two year period to work in the laboratory of Dr. Richard Childs at the National Institutes of Health (NIH). Dr. Childs heads up a research lab, supervising a staff of 15 people at the NIH’s National Heart, Lung, and Blood Institute (NHLB), where over 80% of his research is in kidney cancer. The ACKC-funded researcher will work on an endogenous virus that Dr. Childs’ lab discovered to be expressed in over 70% of clear cell kidney cancers, which, Dr. Childs hypothesizes, may be involved in the pathogenesis of kidney cancer.

Dr. Childs has been at the NHLB for 12 years and most of that time he has been doing allogeneic stem cell transplants on metastatic kidney cancer patients. An allogeneic stem cell transplant is a process whereby a person’s immune system is replaced with that of a tissue matched donor in the hope that the donor’s immune system will recognize the cancer as foreign and will destroy it. Dr. Childs is the leading physician doing stem cell transplants for kidney cancer patients in the United States, having done 74 transplants and having gotten 29 responses including 8 complete responses. The first patient with metastatic kidney cancer to achieve a complete response remains without evidence of tumor now more than 8 years after the transplant

There are a number of theories to support this treatment. One is that the patient’s own immune system may be dysfunctional in that it allowed the cancer to grow in the first place. Another is that the immune system may simply have not recognized the tumor as expressing foreign antigens (an antigen is a substance that provokes an immune response). There are two immune responses that may occur in the patient following a stem cell transplant: graft versus host disease (GVHD) and graft versus tumor response (GVT). In the first case, the donor’s immune system sees the patient’s tissue as a foreign substance and attacks it, causing side effects, which are generally ameliorated by immunosuppressant drugs. After a number of months, GVHD hopefully abates and GVT kicks in to shrink or destroy the tumor.

In a few patients, Dr. Childs observed that despite the fact that no GVHD developed, the tumor shrunk anyway, causing him to hypothesize that the donor’s immune system had recognized antigens on the tumor’s surface that were not present on normal tissue. This led to a search for the antigen, and, after a while, the lab discovered a human endogenous retrovirus (HERV) was actually encoding the antigen, that is, a virus that is part of the human genome but which is only turned on in kidney cancer cells, whereas in normal tissues it is turned off. In the lab’s research, they’ve only found the endogenous retrovirus expressed in clear cell pathologies, where they’ve found it turned on in about 80% of the tumors they’ve examined.

It remains to be demonstrated if this HERV might actually somehow promote or even cause kidney cancer, but, if turning off the virus causes the tumor to stop growing, then Dr. Childs will have proven his hypothesis. If true, drugs can be developed to cure the cancer and a vaccine can be formulated as adjuvant therapy to prevent recurrence of the cancer after a nephrectomy.

Another area of research that Dr. Childs is working on is with Natural Killer (NK) cells. NK cells are lymphocytes, which are a type of white blood cells that play a role in the body’s defenses. One problem with respect to fighting kidney cancer is that NK cells do not efficiently target the tumor and are insufficient in fighting the cancer. Dr. Childs has been experimenting with extracting a patient’s NK cells and multiplying them in the test tube. He then plans to sensitize the tumor to make it more susceptible to NK cell-killing and inject the expanded NK cells (expanded up to 30,000 fold in vitro) back into the patient with the hope of achieving a more effective killing machine. He plans to start a Phase 1 trial treating up to 36 patients with metastatic kidney cancer in 2008.

The ACKC-funded fellow will concentrate his/her efforts on the HERV research. Since we have already raised $55,000 to cover the first year’s grant for the researcher, and in May 2007, Dr. Childs hired a researcher, Elena Cherkasova, an experienced virologist originally from Moscow. ACKC is currently in the process of raising the second $55,000 to cover the grant’s second year.

If you would like to support our campaign to fund a researcher to work with Dr. Childs to help him find a cure for kidney cancer, you can help with a contribution, go to our donation page. If you have any ideas for fundraising that you would like to share with us, contact us at info@ackc.org.