Adoptive cell transfer: New technique could make cell-based immune therapies for cancer safer, more effective

December 16, 2012

A team led by Michel Sadelain, MD, PhD, Director of the Center for Cell Engineering at Memorial Sloan-Kettering Cancer Center, has shown for the first time the effectiveness of a new technique that could allow the development of more-specific, cell-based immune therapies for cancer. Their findings were reported online today in Nature Biotechnology.

Immunotherapies—which make use of patients' own immune that have been augmented in the laboratory—have shown some early success in the treatment of including certain types of leukemia. For most cancers, however, cell-based therapies have been harder to develop, in large part because it has been difficult for investigators to train to specifically attack without damaging normal, healthy cells in the body.

The treatment approach, known as adoptive cell transfer (ACT), involves engineering an immune cell called a T cell. In the ACT process, are removed from a patient and a gene is added to allow the T cells to recognize a certain antigen on the surface of a cell. The enhanced cells are grown in the laboratory and then infused back into the patient to seek out and attack cancer cells.

"We are getting better at working with these T cells and enhancing them so that we can get a powerful immunological response against cancer," Dr. Sadelain says. "The dilemma now is that we are concerned with limiting these responses and making them as targeted as possible to avoid potentially harmful side effects."

Cancer cells overproduce certain , which can help T cells to recognize them, but those same antigens are often found in lower levels on healthy cells. "There are very few antigens, if any, that are found only on cancer cells," Dr. Sadelain explains.

"Now we are bringing in a completely new concept," he adds. "If there is no single unique antigen that is found on the surface of the cancer cell we want to target, we instead create T cells that recognize two different antigens found on the tumor cell—a signature that will be unique to that type of cancer—and only attack cells with both antigens, sparing the normal cells that express either antigen alone."

The new technique makes use of receptors known as chimeric antigen receptors (CARs), which allow T cells to target antigens on the surface of a tumor cell, coupled with another type of receptor called a chimeric costimulatory receptor (CCR), by which the T cells can recognize a second antigen.

The CAR and the CCR work together through a process known as balanced signaling, in which the presence of either antigen on its own is not enough to trigger the immune response. Only tumor cells that carry both antigens will be targeted.

In the study, the team created T cells that carried a CAR for an antigen called PSMA and a CCR for an antigen called PSCA. Both PSMA and PSCA are found on prostate cancer cells. The investigators then generated mouse models of prostate cancer and infused the mice with the engineered cells. They found that the T cells attacked only tumors that carried antigens for both PSMA and PSCA.

"We are the first to test this concept and show that it works," Dr. Sadelain concludes. "We plan to develop clinical trials based on this approach, although we have not yet decided whether the first study will be a trial for prostate cancer or for a different type of cancer using two other antigens. Ultimately, our goal is to create targeted immunotherapies that are both potent and safe for patients."

Explore further: New universal platform for cancer immunotherapy developed

Related Stories

New universal platform for cancer immunotherapy developed

March 5, 2012
(Medical Xpress) -- Researchers from the Perelman School of Medicine at the University of Pennsylvania report this month in Cancer Research a universal approach to personalized cancer therapy based on T cells. It is the first ...

New anti-tumor cell therapy strategies are more effective

October 25, 2012
Targeted T-cells can seek out and destroy tumor cells that carry specific antigen markers. Two novel anti-tumor therapies that take advantage of this T-cell response are described in articles published in Human Gene Therapy, ...

Cloned receptor paves way for new breast and prostate cancer treatment

September 13, 2012
Researchers at Uppsala University have cloned a T-cell receptor that binds to an antigen associated with prostate cancer and breast cancer. T cells that have been genetically equipped with this T-cell receptor have the ability ...

Stem cells, potential source of cancer-fighting T cells

September 20, 2011
Adult stem cells from mice converted to antigen-specific T cells -- the immune cells that fight cancer tumor cells -- show promise in cancer immunotherapy and may lead to a simpler, more efficient way to use the body's immune ...

Recommended for you

Vitamin C may encourage blood cancer stem cells to die

August 17, 2017
Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.