CY and DOX enhance bioactivity of GM-CSF–secreting breast tumor vaccine
MedWire News: Low-dose cyclophosphamide (CY) and doxorubicin (DOX) may augment vaccine-induced HER2-specific immunity in breast cancer patients, say researchers.
Up to 40% of breast cancer patients ultimately relapse, state Leisha Emens, from Johns Hopkins School of Medicine in Baltimore, Maryland, USA, and colleagues.
The best drugs have limited impact on survival in disseminated breast cancer, the researchers note. This has led to research into innovative, active, immune-based therapies, such as vaccines, “that could complement standard breast cancer treatments,” they write in the Journal of Clinical Oncology.
In the present study, 28 patients with metastatic, estrogen-receptor positive and/or progesterone-positive or HER2-positive breast cancer received three monthly granulocyte-macrophage colony-stimulating factor- (GM-CSF)-secreting breast tumor vaccinations with CY on day 1 and DOX on day 7.
The sequence was repeated every 4 to 6 weeks for three cycles and a then a fourth cycle 6 to 8 months later. Six patients received the vaccine alone.
By the end of the study, all 28 patients had received at least one vaccination and 16 had received four.
HER2-specific delayed-type hypersensitivity was induced in five (83%) of the six patients receiving vaccine alone and in seven (32%) of the 22 patients receiving the vaccine with chemotherapy.
Significant HER2-specific humoral immunity (1.13 µg/ml) developed in 17% of patients receiving vaccine only and 32% of patients who received vaccine with any dose of chemotherapy.
The researchers note that the addition of 200 mg/m2 CY had no impact on the rate of HER2-specific antibody responses, but at higher doses the immune response was suppressed compared with vaccine alone.
Conversely, the addition of DOX at 15 mg/m2 suppressed HER2-specific antibody responses, whereas higher doses preserved the antibody responses compared with vaccine alone.
The team says that “the induction of HER2-specific humoral immunity was optimally enhanced by the addition of 200 mg/m2 CY or 35 mg/m2 DOX to vaccination.”
No dose-limiting toxicities were observed.
These findings demonstrate “that GM-CSF-secreting breast tumor vaccine is safe and bioactive, whether or not it is given alone or sequenced with low-dose CY and DOX,” say the researchers.
They conclude that GM-CFS induces HER2-specific immunity in breast cancer that may be augmented by low-dose CY and DOX, but note that “the immunomodulatory activity of CY has a narrow therapeutic window, with an optimal dose not to exceed 200 mg/m2. “
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By Liz Scherer