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.

Reduction in Platelet‐Binding Immunoglobulins and Improvement in Platelet Counts in Patients with HIV‐Associated Idiopathic Thrombocytopenia Purpura (ITP) Following Extracorporeal Immunoadsorption of Plasma Over Staphylococcal Protein A‐Silica

“…Recovery from ITP could not be accounted for by direct quantitative removal of platelet-binding IgG and CIC from patient plasma by perfusion over protein A-silica columns, as the recovery process could be initiated by removal of as little as 1 g of IgG per treatment (19,24). However, an immune modulation model based on removal of IgG-CIC from plasma is consistent with the serologic responses observed in this study.…”

Biological response modifiers in the management of patients with breast cancer

“…However, there must be something more going on, since the administration of serum that has passed over the SPA column frequently produces fevers and chills and systemic reactions, implying that the column has added something to or activated something in the serum rather than merely taken something away. Two recent reports suggest that a small fraction of patients treated with SPA column perfusion, including those with breast cancer, may respond to the therapy [60,61].…”

Therapeutic Apheresis in Malignancy

“…In humans, partial responses have been reported in breast and colon cancers and in Kaposi's sarcoma. The largest clinical trial of SPA therapy in malignancy was reported by Messerschmidt et al (22), in which 12 weekly SPA treatments were given. Of the 87 patients 21 had partial responses, but median duration of the response or survival was not given.…”