Dr. Michael Har-Noy states that the immune mechanism of an allogeneic stem cell transplant has been shown to be effective in killing chemotherapy-resistant metastatic cancer cells despite the presence of immunoavoidance mechanisms, but this immune effect is closely tied to lethal graft versus host disease (GVHD) toxicity, therefore limiting its clinical use.
Immunovative Therapies Ltd., a biotech company in Israel, has developed a proprietary compound, AlloStim™, that was designed to elicit a host anti-tumor response without GVHD side effects. Dr. Michael Har-Noy describes how drug was recently evaluated in an FDA-approved phase I/II trial of 42 late-stage metastatic solid tumor patients with a variety of cell types. Most patients in the trial showed evidence of enhanced survival and immune-mediated tumor destruction without GVHD toxicity. Conventional RECIST criteria overestimated tumor size, as responding tumors swelled and appeared larger on computed tomographic scan.
Serum interleukin 12 (IL-12) levels were identified as a predictor of enhanced survival. Fifty percent of patients treated with Immunovative Therapies’ proprietary compound were IL-12-positive and survived a median of 211 days, as opposed to 131 days for those that were IL-12-negative. Nine of 16 refractory metastatic breast cancer patients were IL-12 positive. The Her2-positive subset of breast cancer patients (five of them) were all IL-12 positive and had a median survival of 416 days, while the 11 Her2-negative patients had a median survival of only 134 days.
Dr. Michael Har-Noy indicates that Her2-positive tumors usually spread faster and have a worse prognosis than Her2-negative cancers. The superior response to allogeneic cell treatment in the Her2 positive metastatic breast cancer patients may be due to high quantities of anti-Her2 antibodies present in this subset of patients. Hypothetically, the allogeneic cell treatment potentiates the ability of these antibodies to cause tumor destruction.
This preliminary report describes a remarkably prolonged survival time in a gravely ill subset of cancer patients with an extremely short life expectancy. Immunovative Therapies is preparing to conduct a randomized, double-blind Phase II/III study of this unique treatment in metastatic breast cancer patients.