The results of an expanded Phase 1 trial showed that some patients treated with a fully human monoclonal antibody developed by Bristol Myers Squibb had a positive response to the effort by the agent, BMS-936558, to prolong the immune system's efforts to fight off renal cell carcinoma without some of the debilitating side effects common to earlier immunotherapies.
Cancer cells have the ability to trick the immune system, the body's self-defence mechanism, which is designed to ward off infections. Immune therapy such as antibody treatment and vaccines is designed to re-educate the body to recognised cancer as an invader.
"We have known for a long time that in certain cases the immune system can be boosted in a way that can create remissions" of hematologic malignancies like leukaemia and lymphoma, says Doctor David F. McDermott. "We have been trying to create the same long term results in solid tumours, which is more difficult."
In this trial, the antibody was designed to block the Programmed Death (PD)-1 inhibitory receptor expressed by activated T cells. PD-1 acts a natural shut off valve for T cells. By blocking its action, these cells can be revived to fight cancer. In the initial portion of the trial, the agent showed "promising" activity in patients with various solid tumours, including metastatic renal cell carcinoma, melanoma and lung cancer.
In an expanded trial, patients received up 10 mg/kg of an intravenous treatment twice weekly, followed by 1 mg/kg. Patients received up to 12 cycles of treatment until either progressive disease, unacceptable toxicity or a complete response was detected.
"These antibodies were developed based on an understanding of how the immune system is not well designed to fight cancer," says McDermott. "Your immune system is in place to help fight off infections. So when you have a viral infection, it will turn on in response to that infection and once it is controlled will shut down. The shut off valves, like PD-1, are actually stronger the pathways that turn on the immune system and this makes cancer difficult to control. The new PD-1 blocking antibody prevents this natural shutoff and allows T-cells to recognize and kill tumours."
He added: "We have seen about 30 per cent of the patients with kidney cancer have major responses to this line of treatment. A similar 30 per cent of melanoma patients have had major response to treatment and there are much more melanoma patients in this study than kidney cancer patients. And maybe 20 per cent or so of patients with lung cancer have had major benefit."
MEDICA.de; Source: Beth Israel Deaconess Medical Centre