Just after chemo and radiation, and just before a bone marrow transplant, a patient’s immune system is on high alert ready to wage war against foreign invaders. While this immune system army in all our body tissues helps protect us against disease, it can also cause major side effects during tissue transplants.
In bone marrow transplants, between 30 to 70 percent of all patients develop a disease caused by the immune system in the donor tissue. Like in a sci-fi horror movie, the tissue transplant starts attacking the patient’s own organs. This graft-versus-host disease (GvHD) means a lifetime of immune suppressant drugs – chemicals that come with their own bag of problems.
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But the Israeli company Enlivex has developed a new trick to help a patient accept foreign tissue more readily, improving the odds and outcomes for people suffering from leukemia, lymphoma and other blood cancers requiring bone marrow transplants.
In early human clinical trials in Israel on 13 people, the Enlivex drug candidate ApoCell was found to “miraculously” take a bone marrow transplant patient out of the danger zone in stages 3 and 4 GvHD, which usually have fatal outcomes.
“Even with the highest match possible you still get high rates of GvHD,” says Alon Moran, the CEO of Enlivex, based in Jerusalem. “When you take a non-match, it is almost certain. Our target is to reduce GvHD incidence and high-stage grading while allowing the beneficial effect of the transplant and its new immune activity help the patient fight the cancer.”
Doctors, he adds, are very much looking for alternatives to immune-suppressants.
Aiming for low grades
GvHD is somewhat similar to solid organ transplant rejection. But in GvHD the new immune system of the graft starts attacks the host (the patient), while in solid organ transplants the patient’s immune system attacks the transplanted organ.
Because GvHD is such a dire problem occurring in more than half of all bone marrow transplants, Enlivex is expecting to speed through regulatory hurdles.
“If we can stop or reduce GvHD and avoid it getting to grades 3 or 4, we can save a life,” Moran says. In the Israeli patient study, none of those treated with effective doses of ApoCell reached stages 3 or 4, as opposed to 50% of the matched historical control group.
GvHD occurs across the board in all kinds of blood-related cancers treated with donor marrow. Its effects are just as pronounced in small children as they are in adults and seniors.
With candor, excitement and reservation, Alon admits that the small study size of patients is too low to make sweeping proclamations about the Enlivex drug candidate, but it does appear to have potential worth investigating further.
How it works
The technology takes advantage of a small window of opportunity – a moment when the immune system is on high alert after the destruction of the patient’s bone marrow, by radiation and chemotherapy, in preparation for the transplant.
Using cells from the donor and treating them with proprietary technology developed at the Hadassah University Medical Center in Jerusalem (and owned by the holding company Hadasit Bio), ApoCell in effect “immunizes” the patient against negative effects from the foreign bone marrow.
ApoCell desensitizes the patient’s immune system. After all, it needs the immune factors in the donor tissue to help the body fight cancer. The drug makes the donor tissue less likely to destroy the patient’s organs, while allowing the regular immune activity against the cancer.
ApoCell’s active ingredients are derived from donor cells that are put into apoptosis, or the early stages of dying.
“In a way, the saying that ‘death brings life’ is really true. The removal of such dying cells in our bodies is critical for homeostasis, a physiological mechanism to reduce immune response. This is what our drug is able to achieve,” Moran tells ISRAEL21c.
He suspects that the Enlivex treatment, administered hours before a transplant, could help in a wide range of auto-immune diseases including Crohn’s and lupus. The Crohn’s application has already been tested in animal models.
“Assuming these results are repeated in a larger study, it will be possible to provide a prophylactic treatment that on one hand allows the transplant to fight the cancer in the body of the patient, and on the other hand, allows for reducing GvHD’s destructive and potentially fatal effect so that the treatment can act as an important component in the success of the bone marrow transplant procedure,” Moran concludes.
Founded in 2005, Enlivex employs a staff of eight. The company is working on study design and approvals to start multi-national phase IIB clinical trials. With about $5 million in funding to date, the company is looking for $4 million to $8 million to continue its operations. It is estimated that ApoCell could be ready within four years if the regulatory hurdles are met according to company milestones.