Many kidney cancer patients benefit from new immune therapy - Track Lighting Spotlights

An antibody that helps a person's own immune system battle cancer cells shows increasing promise in reducing tumors in patients withadvanced kidney cancer , according to researchers at Beth Israel Deaconess Medical Center. The results of an expanded Phase 1 trial presented at the AmericanSociety of Clinical Oncology's annual conference in Chicago, showedthat some patients treated with a fully human monoclonal antibodydeveloped by Bristol Myers Squibb had a positive response to theeffort by the agent, BMS-936558, to prolong the immune system'sefforts to fight off renal cell carcinoma without some of thedebilitating side effects common to earlier immunotherapies. The presentation by David F. McDermott, MD, Director of BiologicTherapy Program at the Beth Israel Deaconess Medical Center CancerCenter and an Assistant Professor of Medicine at Harvard MedicalSchool, highlights one of two key efforts underway to use thebody's own disease-fighting tools against cancer.

Separate work by David Avigan MD, Director of BIDMC's Blood/BoneMarrow Transplant Program, focuses on developing a personalizedvaccine, compromised of the patient's tumor and immune systemagents, to battle kidney cancer. Cancer cells have the ability to trick the immune system, thebody's self-defense mechanism, which is designed to ward offinfections. Immune therapy such as antibody treatment and vaccinesis designed to reeducate the body to recognized cancer as aninvader. "We've known for a long time that in certain cases the immunesystem can be boosted in a way that can create remissions" ofhematologic malignancies like leukemia and lymphoma , says McDermott. "We've been trying to create the same long termresults in solid tumors, which is more difficult." In this trial, the antibody was designed to block the ProgrammedDeath (PD)-1 inhibitory receptor expressed by activated T cells.PD-1 acts a natural shut off valve for T cells. s.


By blocking itsaction, these cells can be revived to fight cancer. In the initialportion of the trial, the agent showed "promising" activity inpatients with various solid tumors, including metastatic renal cellcarcinoma, melanoma and lung cancer . In an expanded trial, patients received up 10 mg/kg of anintravenous treatment twice weekly, followed by 1 mg/kg. Patientsreceived up to 12 cycles of treatment until either progressivedisease, unacceptable toxicity or a complete response was detected.

"These antibodies were developed based on an understanding of howthe immune system is not well designed to fight cancer," saysMcDermott. "Your immune system is in place to help fight offinfections. So when you have a viral infection, it will turn on inresponse to that infection and once it's controlled will shut down.The shut off valves, like PD-1, are actually stronger the pathwaysthat turn on the immune system and this makes cancer difficult tocontrol. The new PD-1 blocking antibody prevents this naturalshutoff and allows T-cells to recognize and kill tumors." McDermott noted that unlike current immunotherapies usinginterleukin-2, patients do not need to be hospitalized and sufferfar less significant side effects such as skin rash or nausea. "We realized that we could this drug at the highest doses withoutdeveloping many significant or too dangerous side effects," saysMcDermott.

"Once we realized the drug was relatively safe to give,we expanded into larger numbers of patients who seem to bebenefiting early on from this treatment." McDermott cautions that it is too early in a Phase I trial,designed principally to test side effects and the best dosage andschedule of treatment, to draw sweeping conclusions from theresults. "We have seen about 30 percent of the patients with kidney cancerhave major responses to this line of treatment. A similar 30percent of melanoma patients have had major response to treatmentand there are much more melanoma patients in this study than kidneycancer patients. And maybe 20 percent or so of patients with lungcancer have had major benefit." Additional References Citations.

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