Killer "T" cells “learn” to hunt down and attack cancer cells, researchers claim.

New wonder drug matches and kills all kinds of cancer — human testing starts 2014

By Michael Blaustein Newyorkpost.com

Stanford researchers are on track to begin human trials of a potentially potent new weapon against cancer, and would-be participants are flooding in following the Post’s initial report on the discovery.

The progress comes just two months after the groundbreaking study by Dr Irv Weissman, who developed an antibody that breaks down a cancer’s defense mechanisms in the body.

A protein called CD47 tells the body not to “eat” the cancer, but the antibody developed by Dr Weissman blocks CD47 and frees up immune cells called macrophages — which can then engulf the deadly cells.

The new research shows the miraculous macrophages effectively act as intelligence gatherers for the body, pointing out cancerous cells to cancer-fighting “killer T” cells.

The T cells then “learn” to hunt down and attack the cancer, the researchers claim.

“It was completely unexpected that CD8+ T (killer T) cells would be mobilized when macrophages engulfed the cancer cells in the presence of CD47-blocking antibodies,” said MD/PhD student Diane Tseng, who works with Dr. Weissman.

The clinical implications of the process could be profound in the war on cancer.

When macrophages present “killer T” cells with a patient’s cancer, the T cells become attuned to the unique molecular markers on the cancer.

This turns them into a personalized cancer vaccine.

“Because T cells are sensitized to attack a patient’s particular cancer, the administration of CD47-blocking antibodies in a sense could act as a personalized vaccination against that cancer,” Tseng said.

The team of researchers at Stanford plan on starting a small 10-100 person phase I clinical human trial of the cancer therapy in 2014.

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Organ transplant recipients face higher cancer risk

CBC News

People who've received a kidney, liver, lung or heart transplant may have double the risk of developing cancer compared with the general population, but the risk is still low overall, a new U.S. study suggests.

Organ transplant recipients are thought to have a higher risk because their immune systems are suppressed by medications to prevent the organs from being rejected and they are more prone to cancers related to viruses such as hepatitis B or C viruses that cause some liver cancers.

"In this large, population-based study of US transplant recipients, we observed a two-fold overall increased risk of cancer," the study's authors wrote in Tuesday’s issue of the Journal of the American Medical Association.

The researchers estimated the risk of developing cancer after a transplant is 0.7 per cent.

"A better understanding of cancer risk in transplant recipients would help clarify the role of the immune system, infections, and other factors in the development of malignancy, and could identify opportunities to improve transplant safety," concluded Dr. Eric Engels of the National Cancer Institute in Rockville, Md., and his colleagues.

Other contributing factors for some cancers may include other effects of chronic immune disturbance or inflammation, underlying medical conditions, or medication toxicity.

The researchers analyzed data on organ transplant recipients and 13 state and regional cancer registries to determine cancer risk in transplant recipients compared with the general population.

The most common transplanted organs in the study were:

• Kidney.
• Liver.
• Heart.
• Lung.

The study included data on nearly 176,000 solid organs transplanted between 1987 and 2008.

Transplant recipients were linked to 10,656 cancer diagnoses during follow-up. The risk was higher for 32 different types of the disease.

The potential reasons for increased cancer risk varied by transplant type. For example, non-Hodgkin lymphoma risk was especially high among lung recipients, possibly as a result of the intensity of immunosuppression or the large amount of tissue they received, the researchers said.

Two cancers showed decreases, breast and prostate. The study's authors acknowledged those decreases could arise from screening before transplant that led to the removal of those cancers. Higher medical surveillance could also be contributing.

This research was funded in part by the U.S. National Cancer Institute.

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Cyclosporine Side Effects Linked to Risk of Cancer After Liver Transplant

AboutLawsuits.com

A study by Dutch researchers seems to indicate that the organ transplant drug Cyclosporine may increase the risk of cancer among liver transplant recipients.

The findings were published in this month’s issue of the medical journal Liver Transplantation, looking at the rate of new cancer malignancies that occur after patients receive new livers. Researchers say the data they collected indicates that cyclosporine cancer risk is dose-specific, meaning that the more of the medication a patient receives, the higher the risk of cancer.

Cyclosporine is an immunosuppressant that helps prevent the body from rejecting transplanted organs by weakening the immune system. It was approved for use by the FDA in 1983 and was originally developed by Sandoz, now known as Novartis, under the brand name Sandimmune.

In the latest study, researchers performed a retrospective analysis on 385 liver transplant patients between 1986 and 2007. They discovered that 50 of those patients, or 13%, developed a de novo (new) cancer after the transplants. When they looked at the therapies the patients had received, researchers determined that the key risk factor appeared to by the use of cyclosporine.

Researchers also found that the cancer risk was highest in patients who received transplants in recent years, and among those under 50 years of age. They determined that the increase was associated with a change in cyclosporine treatment that increased the amount of the drug they were receiving.

The cancers that followed in the wake of cyclosporine treatments were also more aggressive when compared to patients taking other transplant treatments who developed cancer, researchers said.

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Has your life been saved by an organ transplant? "Pay it forward" and help spread the word about the need for organ donation - In the U.S. another person is added to the national transplant waiting list every 11 minutes and 18 people die each day waiting for an organ or tissue transplant. Organs can save lives, corneas renew vision, and tissue may help to restore someone's ability to walk, run or move freely without pain. Life Begins with You

Kimberly Liew, widow of man who died from diseased kidney transplant, fulfilled hubby's dying wish

Egan-Chin/News

Kimberly Liew (r.), with her mother Gim Lian Soh, says all she can do now is 'let go.'

BY PATRICE O'SHAUGHNESSY
DAILY NEWS STAFF WRITER

Kimberly Liew felt good Saturday for the first time in the nearly eight years since her husband died.

"I have a very heavy burden since his death," said Liew, 46, referring to the promise she made her husband, Vincent, on his deathbed.

"He said, 'Please let people know what happened to me so they don't go through this,'" she said.

Liew spoke a day after a Queens jury found NYU Medical Center not liable for her husband's death seven months after he received a kidney from a woman with uterine cancer.

But she said she still felt victory.

"His wish has been accomplished; that is the most important thing. Donor organs and doctors will be more careful ... patients will be more educated. I believe that.

"There's nobody to be blamed for this," she continued in her cheerful way. "It was hard for [surgeon Thomas Diflo] and hard for me. I sent him a card, saying I forgive him. ... I forgave him eight years ago. Letting go is all I can do now."

Liew, 46, said Friday was a "very difficult day, waiting for the verdict. I thought I was going to win the case."

After the jury announced that Diflo did not commit medical malpractice and awarded Liew no damages, she was stunned.

"I didn't know what was going on," Liew said. "I asked my sister-in-law sitting with me, 'Is that the verdict?' and she said, 'Yeah, you lost the case.'"

The verdict marked the end of a long, sad journey. Liew's 37-year-old husband was her life partner and they did everything together, from mundane housework to hanging out at Starbucks to taking vacations.

After his death, "It was very difficult," she recalled, crying. "I became sick. I went to the doctor many times and they couldn't find any diagnosis. My pastor's wife said I needed therapy and she helped me."

She sniffled and said, "Now my eyes are swollen," and laughed slightly.

When her husband received the transplant in April 2002, the couple thought it was the answer to their prayers, but instead it debilitated him.

His widow said Diflo told the patient he had the slimmest chance of contracting uterine cancer and should keep the diseased organ.

Diflo testified that he explained the risks and the patient insisted on keeping the kidney, but the widow disputes that.

The kidney was removed in August, and he died a month later. "I'm thinking how long would he have lived if [Diflo] removed it [right away]," she said wistfully.

She launched her long crusade to sue shortly after her husband died, but says her first lawyer botched the case.

She then went to lawyer Daniel Buttafuoco in 2008.

Liew was seeking $3 million for her husband's pain and suffering. She insists it wasn't about the money, but her husband's message.

"I went to dinner with my family last night, and everybody felt sorry about the verdict," she said, "but Vincent always said, 'God never makes mistakes,' and if He allowed the verdict, I have to accept it. Maybe He has a better future for me."

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Has your life been saved by an organ transplant? "Pay it forward" and help spread the word about the need for organ donation - In the U.S. another person is added to the national transplant waiting list every 11 minutes and 18 people die each day waiting for an organ or tissue transplant. Organs can save lives, corneas renew vision, and tissue may help to restore someone's ability to walk, run or move freely without pain. Life Begins with You

Transplant Patients Have Worse Cancer Outcomes, Analysis Shows

ScienceDaily (May 17, 2009) — After comparing two patient cancer registries—one featuring transplant patients and the other the general population—researchers at the University of Cincinnati (UC) have found that transplant patients experience worse outcomes from cancer.

These results will be published in the May 15, 2009, edition of the journal Transplantation, which is currently in press.

Yun Miao, MD, PhD, Jason Everly, PharmD, Steve Woodle, MD, and colleagues at UC compared lung, colon, breast, prostate, bladder, kidney and skin cancer data in 635 adult transplant recipients from the Israel Penn International Transplant Tumor Registry with that of about 1.2 million adults from the general population in the Surveillance, Epidemiology and End Results (SEER) database.

"It has been known for some time that transplant recipients are at an increased risk of developing cancer, but the outcomes of cancers that arise in organ transplant recipients have not been defined," says Woodle, professor and chief of transplant surgery and co-author of the study.

"In this study, we wanted to examine the influence of transplantation on the outcomes of individual types of cancers arising in organ transplant recipients," adds Miao, co-author and research fellow in the division.

The Israel Penn International Transplant Tumor Registry is the largest and most comprehensive transplant tumor registry in the world and was created by doctors at the UC College of Medicine.

The SEER registry collects information on cancer incidence, survival and prevalence for roughly 26 percent of the United States population and compiles reports and statistics based on this information along with cancer mortality rates for the entire nation.

A comparison of results in transplant recipients to the general population also demonstrated that transplant patients were more likely to have early stage renal cell (kidney) cancer and more advanced colon, breast, bladder and skin cancer at the time of diagnosis.

Disease-specific survival was worse in the transplant population for each of these seven cancers analyzed and was a negative risk factor for survival.

Now, researchers want to conduct further studies to find out why this may be the case.

"Transplant patients receive immunosuppressive therapies to prevent them from rejecting transplanted organs," says Woodle. "We want to see if immunosuppressive therapies contribute to the poorer outcomes in transplant recipients."

He says the worse outcomes in transplant recipients may have occurred because this population is not as healthy as the general population or because their cancers may be more aggressive as a result of their immunosuppression treatments.

"Some of our data supports this premise, as the extent of the cancers at diagnosis were greater in the transplant recipients," Woodle continues. "This was surprising since transplant recipients are generally followed more closely than the general population."

Everly, co-author and board-certified oncology pharmacist in the division, says that this data may change the way physicians screen transplant patients for cancer.

"We found that most cancers developed within five years following transplantation," he says, noting that more frequent and detailed checks should be made in order to catch the cancer in its earliest stages. "This may alter the way doctors should screen these patients for cancer."

This study was investigator-initiated and supported by research grants from Astellas Pharmaceuticals.

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Organ Transplants Linked to Cancer

(Ivanhoe Newswire) -- Organ transplants can save lives, but new research shows they might also put recipients at risk of developing cancer.

New research at the Harvard Medical School revealed the immunosuppressive drug cyclosporine ramps up vascular endothelial growth factor (VEGF), causing new blood vessels to grow and feed tumors. Tumors that develop after a transplant can come from three sources: viruses from the organ donor, pre-existing cancer or recurrence of previous cancer.

The study revealed a potential treatment: anti-VEGF therapy, which could inhibit cancerous cell growth. For the 15 to 20 percent of patients who develop cancer in the decade that they received transplants, this could be great news. Researchers found the anti-VEGF therapy drastically reduced tumor growth in mice implanted with human kidney cancer cells.

VEGF expression is necessary in the immediate stage after transplantation, but after organ stabilization, lowering VEGF expression is important to “prevent tumor growth and keep cancer at bay,” Soumitro Pal, Ph.D., an assistant professor at Harvard Medical School’s Transplantation Research Center at Children’s Hospital in Boston, was quoted as saying. He added, “We would need to figure out how to balance benefit and risk to keep cancer at bay.”

SOURCE: Cancer Research, 2008;68,5689-5698

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