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Home > News and Publications > JHM Publications > Promise and Progress > Promise & Progress: Special Issue Bloomberg - Kimmel Institute for Cancer Immunotherapy
Promise and Progress - Lessons from the First Immune Therapy
Promise & Progress: Special Issue Bloomberg - Kimmel Institute for Cancer Immunotherapy
Issue No. 2016
Issue No. 2016
Lessons from the First Immune Therapy
Date: March 23, 2016
Some of the earliest research at the Kimmel Cancer Center that focused on the immune system was in blood and bone marrow cancers and bone marrow transplantation. Cancers of the blood and bone marrow, such as leukemia, lymphoma, and multiple myeloma, provided a unique perspective of normal immune cells, malignant ones, and the magnitude of the immune system’s power.
In most cancers, the goal is to engage the immune system, but in bone marrow transplant, where the patient’s cancer-filled bone marrow is replaced with healthy marrow from a donor, the goal is to disengage—well at least a little. The reason is a serious complication of bone marrow transplant known as graft versus host disease (GVHD), a destructive immune attack against the patient’s organs and tissue. The transplanted marrow sees its new host as foreign and wages an assault that can be as lethal as cancer.
Veteran cancer immunology leader Drew Pardoll first observed its wrath as an oncology trainee treating a young girl dying from severe GVHD. It was a defining moment for the young physician scientist. “I realized that the immune system was probably the most powerful anticancer weapon we have,” says Pardoll. “If we learned how it worked and could focus it more precisely against cancer, I believe it could be more powerful than any drug.”
Pardoll decided to focus on deciphering how the immune system worked, while Kimmel Cancer Center bone marrow transplant experts began solving the problem of GVHD in what could be considered one of the first immune success stories in cancer treatment.
Making Bone Marrow Transplant Safe and Available to All
For decades GVHD prevented bone marrow transplants from being performed on patients who did not have a donor with a nearly identically matching immune system, usually found in a brother or sister A large national registry matched some of these patients with unrelated donors, but most grew sicker and many died waiting for a match to be found. As a result, only about one-half of patients were candidates for the potentially curative therapy. Minorities suffered the most. African-American patients who did not have a match in their family, had less than a 10 percent chance of finding a donor in the unrelated registry.
Pioneering discoveries led by Kimmel Cancer Center investigators Richard Jones, Ephraim Fuchs and Leo Luznik have now made it possible for almost any patient to receive a transplant. The research that led to this breakthrough focused on immune cells known as T cells and technologies to remove these cells from the donor marrow. Clinical studies showed that when the T cells were removed, patients did not get GVHD, but their cancers sometimes came back. It was one of the first observations of the immune system’s ability to kill cancer cells. The challenge was to remove a precise amount of T cells—small enough to avoid the most severe cases of GVHD yet a large enough number to allow the immune system to keep the cancer from coming back.
It turns out that the same drug used to treat patients before bone marrow transplant could be given post-transplant to limit GVHD without hampering the T cell’s ability to mop up any surviving cancer cells. This discovery led Kimmel Cancer Center experts to develop a new type of bone marrow transplant, known as a haploidentical or half-identical transplant.
This breakthrough approach developed at the Kimmel Cancer Center, almost all parents, siblings, and children of patients—and sometimes even aunts and uncles, nieces and nephews, half-siblings, and grandparents or grandchildren—can safely serve as donors. Now, almost every patient who needs a bone marrow transplant can find a matching donor. Since developing the treatment more than a decade ago, Kimmel Cancer Center experts have performed more than 600 half-matched transplants for adult and pediatric leukemia and lymphoma.
These clinical studies have proven so successful, with safety and toxicity comparable to matched transplants, that the therapy is now used to treat chronic but debilitating noncancerous diseases of the blood in adults and children, such as sickle cell anemia and severe autoimmune disorders. Web Exclusive: Read Nicholas’ Story
More recently, a revolutionary study using half-matched transplants to improve the effectiveness and safety of solid organ transplants with living donors has begun. Kimmel Cancer Center researchers are collaborating with transplant surgeons to begin a combined kidney/half-identical bone marrow transplant. Since the patient and donor would have the same immune system, it could essentially eliminate organ rejection and a lifetime of antirejection drugs.
If successful, this important work will conquer the transplantation barrier—rejection—and what they learn could be applied to all solid organ transplants. It also facilitates the research being done in regenerative medicine where work to grow transplantable tissue and organs would ultimately be of no clinical use without the means to successfully and safely transplant them into humans.
Articles in this Issue
- Construction Begins On New Skip Viragh Outpatient Cancer Building
- Sidney Kimmel Helping Others
- Bloomberg ~ Kimmel Institute Cements Progress in Cancer Immunotherapy
- McConkey Named Director of Greenberg Bladder Cancer Institute
- Swim Across America Baltimore Raises Record Funds
- Margareta Augustine Fellowship Supports Young Investigators
- Patients Kept Cozy This Winter