Protein A immunotherapy in the treatment of cancer: An update

Protein A, a naturally occurring Staphylococcus aureus cell surface protein, has the unusual property of binding circulating immune complexes and immunoglobulin G with high avidity. CIC have played a major role in cancer-associated immunosuppression. Thus, removal of the immunosuppressive agents, ie, the CIC, may lead to a modulation of the immunosuppression and a liberation of the immune system to perform an antitumor effect. In animal studies, protein A has been used in extracorporeal immunoadsorption columns and treatments have resulted in tumor shrinkage and antiviral responses. Our group developed a multicenter clinical trial to assess toxicity and antitumor responses with this biologic response modifier alone. This is an update of our original trial. We have now treated 142 patients for a total of 1,306 treatments. The patients consisted of 74 males and 68 females. Their age ranged from 7 to 83 years, with a mean of 50 years. The Karnofsky performance index values ranged from 40 to 95, with a mean of 80. Patients who received seven or more treatments were considered eligible for tumor response assessment, and all patients with one or more treatments were eligible for toxicity assessment. Thus, there were 101 patients eligible for tumor response and 142 eligible for toxicity response. The total response rate was 22 patients or 21.8% (partial remission [PR], 12 patients, 12%; <PR, 10 patients, 10%). Response rates were similar in the 13 treatment centers. Toxicity was assessed in 142 patients. One thousand three hundred six treatments were assessed for treatment toxicity. Side effects consisted of chills (28%), fever (28%), pain (16%), nausea (10%), respiratory (9%), tachycardia (7%), vomiting (5%), hypertension (5%), hypotension (4%), headache (4%), joint pain (4%), rash (2%), flushing (1%), diarrhea (1%), itching/hives (1%), pain at tumor site (1%), bloody nose (1%), and cramps, fatigue, blurred vision, gastritis (all <1%). Three patients had side effects that resulted in termination of the procedure, one as a result of pain and two secondary to rash development. No treatment deaths occurred. Overall the procedure was well tolerated by patients in an outpatient setting. In conclusion, this study demonstrates that extracorporeal immunoadsorption with protein A columns can result in tumor responses in this phase I-II trial. This is a US government work. There are no restrictions on its use.