Thursday , July 29 2021

Studies aim to cure blood cancer with transplants that can block HIV too

Dr. Filippo Milano, associate director of the Cord Blood Program in Hutch, was awarded a $ 1 million grant for trials from National Heart, Lung, and Blood Institute.

For leukemia patients who are seriously ill, transplantation may be their best hope. However, Milano said that because blood cancer patients with HIV are considered to have active infections that place them at a higher risk of complications, they have difficulty meeting the qualifications in many centers for conventional bone marrow or blood stem cell transplants.

The Milano Pioneering Central Cord Blood Program at Fred Hutch is accustomed to finding options for blood cancer patients who cannot find a suitable donor for bone marrow transplantation or blood stem cells. Cord blood, which contains immature blood cells tends to attack the patient's own tissue, can be an alternative for HIV-positive leukemia patients.

"We did not do this trial to cure HIV," Milano said. "We are doing it to cure patients with hematological malignancies and HIV infection simultaneously."

Mutations close the molecular door to HIV

But this trial also offers a tantalizing bonus: The researchers plan to offer this patient's cord blood from about one in 100 donors who are naturally resistant to HIV. As a result, these leukemia patients will appear with a person's immune system that will not be susceptible to viruses. The hope is that this HIV-resistant immune system will eventually get rid of the remnants of the remaining HIV, which can roar back without undisturbed antiretroviral drugs.

Until now, there is only one person in the world who is generally recognized as being cured of HIV: Seattle-born Timothy Ray Brown. While living in Germany in 2007, Brown – whose HIV was controlled by antiviral drugs – received the first bone marrow transplant for leukemia. With a hunch, doctors use cells from donors that carry HIV resistance mutations in genes that affect proteins called CCR5.

In most people, the CCR5 operates as a kind of molecular door. HIV can open this door open and enter immune cells. But 0.8 percent of the world's population inherits from their mothers and fathers genetic mutations that effectively close this door, and some of these lucky people are naturally resistant to HIV. From donors like that Brown accepted his new immune system, and 11 years later, he still did not have a trace of HIV and his leukemia remained in remission. Until now, no other patient who received the transplant managed to remain HIV negative. The experiment in Milano will try to replicate Brown's experience using cord blood.

Experimental cord blood products are the key to testing

In this experiment, patients will receive only one unit of cord blood, which has a very small number of adult blood cells. However, each patient will also receive a dose of an experimental product, dilububel, from Nohla Therapeutics. The Seattle company was founded by researcher Fred Hutch, Dr. Colleen Delaney, Madeline holder Dabney Adams, Endowed Chair at AML Research and director from Hutch & # 39; s Cord Blood Program.

Derived from cord blood cells multiplied in the laboratory, experimental drugs were given with transplant cells to protect patients from infection until transplant cord blood cells had time to set up shop as a functioning immune system.

"The number of stem cells in cord blood is very limited, especially for adults, because they come from the baby's umbilical cord," Milano said. "Product Colleen buys time for cord blood to enter and protect patients."

By entering Nohla's medicine in the trial, cells from only one umbilical cord donated are needed, not two that are usually needed in cord blood transplantation. As a result, it is important to find only one donor carrying mutations, increasing the opportunity to meet the needs of patients seeking HIV blocking mutations in transplants. Milano calculates that there are around 6,500 units stored in cord blood banks throughout the world. The hope is to find several dozen units, which are stored at the Cleveland Cord Blood Center, which may be very suitable for this trial.

The plan is to ask patients to be treated in one of the five US cancer centers that also have expertise in HIV care.

"We will have a world-class cancer doctor who works with world-class HIV experts," Milano said.

Participating hospitals that work with Hutch include UW Medicine and Seattle Children's Hospital; Case Western Reserve University / Cleveland Medical Center University Hospital; Children 's Research Institute / Children's National Medical Center, Washington, D.C .; Memorial Sloan Cancer Center Kettering, New York; and the University of California, San Francisco Medical Center.

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