title: Protein A immunoadsorption in the treatment of malignant disease.
abstract: Circulating immune complexes (CIC) are known to be present in cancer patients and are responsible for much of the cancer-associated immunosuppression. Removal or modulation of these "blocking factors" can reverse the immunosuppression. Protein A from Staphylococcus aureus has the unusual property of binding to CIC with high avidity. Use of protein A as an immunoadsorbent in extracorporeal immunotherapy affinity columns has resulted in antitumor and antiviral responses in animals. Our group developed a multicenter trial to assess toxicity and antitumor response with this biologic response modifier alone. Overall, 24% (21 of 87 patients) had objective tumor regressions including both partial responses (PR) and less than PR. No complete responses (CR) were observed. Responses were observed in acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (six of 17 PR; two of 17 less than PR; overall, 47%), breast adenocarcinoma (five of 22 PR; three of 22 less than PR; overall response, 36%), colon adenocarcinoma, (one PR, one less than PR; overall response, 11%), and non-oat cell lung carcinoma (two of seven less than PR). The procedure was well tolerated and could be performed on an outpatient basis. No adverse reaction was observed in 735 of 1,113 treatments (66%). The most common adverse effect was an "influenza-like" syndrome consisting of fever and chills. Pain was present in 12% of the patients. There were no study-related deaths. Serum IgG and CIC levels did not statistically change due to therapy in responding or nonresponding patients. Complement levels remained within the normal range. Liver and renal tests remained stable throughout the study. In summary, protein A immunoadsorption of plasma is well tolerated in the outpatient clinic, has demonstrated antitumor activity in resistant solid tumors, and functions as a biologic response modifier.
authors.affiliation: Protein A Clinical Trial Group, Wilford Hall USAF Medical Center, San Antonio, TX.
authors.forename: G L
authors.initials: GL
authors.lastname: Messerschmidt
authors.forename: D H
authors.initials: DH
authors.lastname: Henry
authors.forename: H W
authors.initials: HW
authors.lastname: Snyder
authors.forename: J
authors.initials: J
authors.lastname: Bertram
authors.forename: A
authors.initials: A
authors.lastname: Mittelman
authors.forename: S
authors.initials: S
authors.lastname: Ainsworth
authors.forename: J
authors.initials: J
authors.lastname: Fiore
authors.forename: M V
authors.initials: MV
authors.lastname: Viola
authors.forename: J
authors.initials: J
authors.lastname: Louie
authors.forename: E
authors.initials: E
authors.lastname: Ambinder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care; D000936:Antigen-Antibody Complex / Q000032:analysis*; D001804:Blood Transfusion, Autologous; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007163:Immunosorbent Techniques; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013205:Staphylococcal Protein A / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D013205:Staphylococcal Protein A