Navigation Links
T vs. B: Re-engineered human T cells effectively target and kill cancerous B cells

PHILADELPHIA − Human white blood cells, engineered to recognize other malignant immune cells, could provide a novel therapy for patients with highly lethal B cell cancers such as acute lymphoblastic leukemia (ALL), according to researchers at Memorial Sloan-Kettering Cancer Center (MSKCC). By administering repeated doses of T cells designed to express an artificial receptor which recognizes human B cells, the researchers were able to eradicate cancer in 44 percent of mice bearing human ALL tumors.

Their findings, published in the September 15 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, show that modified T cells the white blood cells that actively fight infections can be effective in fighting malignancies associated with B cells (immune cells that create antibodies) such as chronic lymphocytic leukaemia (CLL), ALL, non-Hodgkin's lymphoma (NHL). The researchers have an ongoing study using these T cells in CLL, and have recently begun the planning stages for a trial in patients with ALL.

The immune system has evolved to police the body for infections and diseased cells, but it has a difficult time recognizing malignant cells since they largely appear normal to the immune system, said lead study author, Renier J. Brentjens, M.D., Ph.D., medical oncologist in the Leukemia Service at MSKCC. The idea is that we can take a patients own T cells, re-educate them by inserting a gene into them that will enable them to produce a receptor to recognize B cell cancers, and then return them to the patient where they should be able to attack and kill the tumor cells.

Because the technique uses a patients own T cells, there is little risk of compatibility issues or rejection, as there might be with human stem cell transplant, Dr. Brentjens adds. Human stem cell transplant, following radiation or chemotherapy, is currently incorporated into the treatment of several B cell malignancies.

In order to get T cells to recognize B cells, Dr. Brentjens and his colleagues created a gene that encodes for a cell-surface protein an artificial T cell receptor called a chimeric antigen receptor -- designed to specifically bind to CD19, a molecule found on the surface of B cells and B cell cancers. Antigen receptors are what allow T cells, in combination with other parts of the immune system, to recognize and attack infected or malignant cells. This chimeric gene, formed from active portions of several immune system-related genes, creates the chimeric antigen receptor protein called 19-28z, which does not require other co-stimulatory signals to fully activate T cells, according to Dr. Brentjens.

Dr. Brentjens and his colleagues used an engineered retrovirus to insert the chimeric antigen receptor gene into T cell DNA. Retroviruses insert DNA derived from their RNA into that of a host cell, which then uses viral vector-encoded genes to make specific proteins. In this case, the researchers infected healthy T cells with modified retroviruses containing the gene that codes for 19-28z. The T cells internal protein-making facilities then produce the chimeric receptor as if it were one of its own natural antigen receptors.

In Clinical Cancer Research, the MSKCC researchers detail the creation of 19-28z, their second generation chimeric antigen receptor, and its effectiveness in stimulating human T cells both in culture and in an animal model of human cancer. They also compared T cells engineered with 19-28z to T cells engineered with a first generation chimeric antigen receptor, lacking the co-stimulatory signal found in 19-28z. Their results showed that the second generation 19-28z receptor was superior to the first generation receptor, and that this T cell therapy works best when administered to mice through multiple weekly injections.

The repeated boosts of new T cells during therapy to improve T cell persistence enhances the efficacy of these T cells in eradicating cancerous B cells, said Dr. Brentjens. This concept of T cell persistence being critical to treatment efficacy is one we are further investigating in current and upcoming clinical trials.

The results have given the researchers further evidence that the technique will work in humans. When transplanted back into a patient, these engineered T cells could then attack and kill tumor cells bearing the CD19 protein. CD19 is not found on the surface of bone marrow stem cells, so these modified T cells are reasonably safe since they should not attack other blood forming cells in the bone marrow following treatment, Dr. Brentjens said.

Based on the results of their findings, the MSKCC researchers are currently conducting a clinical trial using this method in patients with chemotherapy-resistant CLL. CLL is currently considered an incurable cancer, Dr.

Brentjens said, although the disease generally progresses slowly.

Contact: Greg Lester
American Association for Cancer Research

Related medicine news :

1. Human Genome Project Achieves Technological Triumph
2. First Vaccine Designed for Africa Cleared for Testing in Humans
3. Controversial deal on public access of the human genome map
4. Man against HIV – new vaccine ready for human trials
5. Scientists plan human cloning clinic in the United States
6. FDA approves Phase 0 trial which tests experimental drugs on humans
7. Human gene number increases
8. First human clone is near
9. Water regulation in humans
10. Fossil teeth and human development
11. Scientists found ancient Human Germ Killer
Post Your Comments:
(Date:11/28/2015)... ... 2015 , ... Beginning November 30th at 6:00 a.m. EST until 11:59 p.m. EST, ... savings of up to 20% off orders $80 or more to free gifts with purchases, ... hours. , As a competitive e-commerce website for skin care and cosmetic needs, customers will ...
(Date:11/27/2015)... ... , ... According to an article published November 13th on, ... D.C. revolved around the fact that proper dental care, both at-home and in the ... between periodontal disease (more commonly referred to as gum disease) and diabetes. According to ...
(Date:11/27/2015)... ... 27, 2015 , ... The rapid speed at which Americans ... more care is needed, especially with Alzheimer’s, dementia and other cognitive conditions becoming ... The forgotten part of this equation: 80 percent of medical care occurs in ...
(Date:11/27/2015)... ... November 27, 2015 , ... "When ... said an inventor from Hillside, N.J. "Many people catch diseases simply from sitting ... individuals will always be protected from germs." , He developed the patent-pending QUDRATECS ...
(Date:11/27/2015)... ... November 27, 2015 , ... ProSidebar: Fashion is a set of ... With ProSidebar: Fasion, video editors can easily add an informative sidebar to any FCPX ... Utilize presets featuring self-animating drop zones, lines, bars, and text with the ease ...
Breaking Medicine News(10 mins):
(Date:11/29/2015)... Royal Philips  (NYSE: PHG, AEX: PHIA) revealed a portfolio ... Society of North America Annual Meeting (RSNA), beginning today ... Chicago . Visitors to the Philips booth ... integrated Diagnostic Imaging, Clinical Informatics, Image Guided Therapy and ... and create a superior patient experience. ...
(Date:11/27/2015)... Une nouvelle approche consistant ... contre le cancer avancé.    --> ... au traitement photodynamique au Bremachlorin contre le cancer ... nouvelle approche consistant à combiner l,immunothérapie au traitement ...    Clinical Cancer Research . ...
(Date:11/27/2015)... Nov. 26, 2015 ... of the "2016 Global Tumor Marker ... Volume and Sales Segment Forecasts, Innovative Technologies, ... report to their offering. --> ... the "2016 Global Tumor Marker Testing ...
Breaking Medicine Technology: