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Richard W. Childs, M.D.

Laboratory of Transplantation Immunotherapy

Richard W. Childs, M.D.
Senior Investigator
Laboratory of Transplantation Immunotherapy


Building 10-CRC Room 3-5330
10 Center Dr
Bethesda, MD 20892
P: +1 301 451 7128
F: +1 301 480 2664
childsr@nhlbi.nih.gov

Background

Richard Childs earned a B.S. in biology in 1987 from Georgetown University and received an M.D. in internal medicine from Georgetown University Medical School in 1991. He completed his internship and residency from 1991 to 1994 at the University of Florida Medical Center. He joined the NHLBI in 1995 for an oncology and hematology fellowship. In 1999 he became an Investigator with the Hematology Branch and in 2007 became a Senior Investigator and Chief of the section of Transplantation Immunotherapy. He is currently an Active Duty Captain with the U.S. Public Health Service. In 2010 he received the U.S. Public Health Service Distinguished Service Award from the Surgeon General for pioneering tumor immunotherapy research. Dr. Childs has received numerous other awards including 4 NIH Bench to Bedside Awards. He has authored over 130 manuscripts and more than 20 book chapters. Dr. Childs is a current member of the American Society of Clinical Investigation, American Association for Cancer Research, American Society of Clinical Oncology, American Society of Hematology, International Society for Cellular Therapy, and American Society of Clinical Investigation. Dr. Childs has four active FDA investigational new drugs in the application process and holds 3 patents.

Research Interests

It is now believed that many nascent cancers never proliferate to life-threatening proportions because of routine surveillance by the immune system. Dr. Childs’s translational research program is focused on finding ways to adapt and enhance immune cells to attack even the most entrenched cancers. In particular, he has focused on allogeneic stem cell transplantation and tumor immunology to treat aplastic anemia, hematological malignancies, and solid tumors.

Dr. Childs was the first to establish that T-cells from matched donors could cure patients with metastatic renal cell carcinoma. This “graft-vs-solid tumor” effect, published in the New England Journal of Medicine in 2000, defined a new therapeutic application for allogeneic hematopoietic stem cell transplantation. Subsequently, his group characterized the immune mechanisms mediating this effect and in experiments using allogeneic T-cells from responding patients, discovered a novel human endogenous retrovirus expressed in kidney cancer that serves as a target for human immune cells. His laboratory then characterized the molecular mechanisms leading to the selective transcription of this provirus in the clear cell subtype of kidney cancer. The laboratory continues to identify antigens that are derived from the endogenous retrovirus that may serve as a target for T-cell immunotherapy. They are also exploring peptides and proteins that could potentially serve as a vaccine to generate T-cell mediated rejection of the tumor.

A major focus of the Childs laboratory is on the potentiation of natural killer (NK) cells, which are the key immune cell effectors of cancer cell death. NK cells are dominated by inhibitory pathways that under normal circumstances limit their lethality. Dr. Childs has explored a number of methods to block this inhibition of NK cells in tumors. Recently, his team has discovered that exposing tumors to proteasome inhibitors sensitizes them to NK cells through expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). He and his colleagues are also developing methods to increase the expression of adhesion molecules on NK cells that will allow them to better access the bone marrow microenvironment where hematologic malignancies originate.

Information gleaned from Dr. Childs’s translational research has defined novel pathways through which malignancies may be targeted by the human immune system. Dr. Childs currently has a number of transplant protocols underway that are based on research conducted in his laboratory. Recently, he has focused on developing methods to improve the outcome of allogeneic stem cell transplantation for aplastic anemia where immunosuppressant therapies have failed and to improve the outcome for patients who lack a matched donor. Dr. Childs and his colleagues have developed and implemented a protocol that combines two stem cell sources: transplanted umbilical cord blood and cells purified from a partially matched relative (parent, child, or un-matched sibling) to treat patients with aplastic anemia that are at high risk of graft rejection. This pilot trial has shown early signs of sustained donor engraftment.

Selected Publications

Inactivation of the von Hippel-Lindau tumor suppressor leads to selective expression of a human endogenous retrovirus in kidney cancer.
Cherkasova E, Malinzak E, Rao S, Takahashi Y, Senchenko VN, Kudryavtseva AV, Nickerson ML, Merino M, Hong JA, Schrump DS, Srinivasan R, Linehan WM, Tian X, Lerman MI, Childs RW.
Oncogene. 2011 Nov 24;30(47):4697-706.
[Text Abstract on PubMed]

Bortezomib treatment and regulatory T-cell depletion enhance the antitumor effects of adoptively infused NK cells.
Lundqvist A, Yokoyama H, Smith A, Berg M, Childs R.
Blood. 2009 Jun 11;113(24):6120-7.
[Text Abstract on PubMed]

Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells.
Takahashi Y, Harashima N, Kajigaya S, Yokoyama H, Cherkasova E, McCoy JP, Hanada K, Mena O, Kurlander R, Tawab A, Abdul T, Srinivasan R, Lundqvist A, Malinzak E, Geller N, Lerman MI, Childs RW.
J. Clin. Invest. 2008 Mar;118(3):1099-109.
[Text Abstract on PubMed]

Reduction of GVHD and enhanced antitumor effects after adoptive infusion of alloreactive Ly49-mismatched NK cells from MHC-matched donors.
Lundqvist A, McCoy JP, Samsel L, Childs R.
Blood. 2007 Apr 15;109(8):3603-6.
[Text Abstract on PubMed]

Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation.
Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Barrett AJ.
N. Engl. J. Med. 2000 Sep 14;343(11):750-8.
[Text Abstract on PubMed]

Richard W. Childs' Full List of Publications

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Last Updated: April 26, 2013

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