In a newly published study, researchers found a robust and selective immune response in some patients who received, immediately after the transplant, numerous doses of a “personalized” tumor vaccine consisting of their own inactivated leukemia cells coupled with an immune stimulant.
Patients with severe chronic lymphocytic leukemia (CLL) frequently get donor transplants, which effectively “reboot” their immune defenses, allowing them to combat and perhaps cure the illness. However, these individuals have a high recurrence rate, and the immune cells that are transplanted may damage normal tissues, resulting in graft-versus-host disease (GVHD).
For advanced CLL, therapeutic choices are limited. Traditional transplants, which include high doses of pre-transplant chemotherapy to eradicate as much leukemia as possible, have shown to be too toxic for older patients and those with co-existing illnesses.
Researchers have developed reduced-intensity conditioning (RIC) regimens during the last decade, which use lower chemotherapy dosages that are more bearable but rely solely on the function of the donated immune cells to fight leukemia. This is usually insufficient to keep cancer at bay in the long run, and the illness develops.
According to senior author Catherine Wu, a Harvard Medical School associate professor of medicine, “our results show that autologous tumor cell vaccination is a viable method to enhance long-term leukemia control” following donor transplants. “Despite the fact that this was a phase 1 research with insufficient power to investigate clinical effectiveness, we saw intriguing clinical activity.”
Furthermore, research has revealed that the identifying antigens on the surface of CLL cells in different individuals might differ, implying that they have “personal tumor antigens,” according to the researchers.
“Vaccination with autologous irradiated leukemia cells” — the patient’s own stored leukemia cells — “is an attractive approach to expand leukemia-reactive T cells based on these principles, because this vaccine formulation reliably includes personal tumor antigens,” according to the researchers.
The researchers combined the patients’ irradiated leukemia cells with cells that generate GM-CSF to create the vaccine, which they then injected back into the patient. Immune T cells respond strongly to the combination, and the unique antigens on the injected leukemia cells guide the T cells to kill identical leukemia cells wherever they are found in the body.
The vaccination was given between 30 and 100 days following the transplant in the phase 1 study, with some patients receiving up to six doses. Twenty-two individuals with advanced, aggressive CLL were recruited in the research. At the time of transplant, thirteen of the patients had signs of leukemia in their bone marrow.
The vaccination was not given to four individuals because they developed GVHD after the transplant. The remaining 18 patients got at least one vaccine dose; seven individuals discontinued vaccination after developing GVHD.
The majority of patients exhibited indications of clinical response six months after transplantation: ten had full remissions and six had partial remissions; an additional patient had an early complete response but later relapsed at four months. Thirteen patients (72 percent) were in continuous full remission after a median follow-up of 2.9 years, one patient had stable disease, three patients acquired progressive disease, and two of those patients died.
According to the authors, the findings back up the safety and biological activity of entire tumor-cell vaccination in hematological malignancies, and that administering the vaccine soon after transplant was crucial to its efficacy. Furthermore, they claimed that Dana-Farber scientists developed GM-CSF-secreting “bystander” cells that may be utilized against lymphoid malignancies – something that had previously been impossible.