Ex vivo perfusion of plasma over protein A columns in human mammary adenocarcinoma. Role of the Fc‐binding capacity of protein A in the side effects and the tumoricidal response

Abstract

Plasma of twelve patients presenting with a metastic mammary adenocarcinoma was perfused ex vivo over columns of protein A covalently linked to crystalline silica. The plasma of seven patients (group A) was perfused over columns of protein A exhibiting a normal Fc-binding capacity and the plasma of five (group B) over columns of protein A in which the Fc-binding capacity was destroyed. In group A, all patients experienced acute, easily manageable, side effects (hypotension, chills, mild fever, leucocytosis and pain in tumour sites) during or immediately after the immunoadsorption procedures, and three exhibited an objective partial regression after two to five sessions. In contrast, none of the patients from group B developed any acute side effects and all showed evident progression of their disease during the treatment. Tumour cells in all stages of destruction, sometimes surrounded by extensive fibrosis, were seen in biopsies of patients A. However, focal areas of active tumour proliferation were always present in these patients. These data confirm that ex vivo perfusion over protein A columns of plasma from patients with cancer can induce a tumoricidal response in some instances and show that the Fc-binding capacity of protein A is most probably responsible for the necrolytic response and the side effects.

Fast and highly efficient purification of 6×histidine-tagged recombinant proteins by Ni-decorated MnFe2O4@SiO2@NH2@2AB as novel and efficient affinity adsorbent magnetic nanoparticles

“…This protein is a cell wall component of the bacterium Staphylococcus aureus that binds specically to many mammalian immunoglobulins, most markedly IgG and is utilized for oriented immobilization of antibodies from different sources. [36][37][38] Here, Ni 2+ was modied on the surface of MnFe 2 O 4 @ SiO 2 @NH 2 @2AB and the application of these magnetic nanoparticles was investigated in purication of 6Âhistidine-tagged recombinant protein-A from crude E. coli lysate as depicted in Scheme 2. MnFe 2 O 4 @SiO 2 @NH 2 @2AB-Ni magnetic nanoparticles were added to the Soluble Cell Extract (SCE) and the mixture was incubated for 30 min with continuous shaking.…”

Ex vivo perfusion of plasma over protein A columns in human mammary adenocarcinoma. Evidence for a protein A leaking by radioimmunoassay

“…The plasma of twelve patients presenting with a breast adenocarcinoma and metastatic lesions was perfused e x vivo over protein A columns of about 100 ml as previously described [2]. The plasma of seven patients (group A) was perfused over columns containing 200 mg of 'native' protein A, i.e., protein A exhibiting a normal Fc-binding activity, and the plasma of five patients (group B) over columns containing 200 mg of 'denatured' protein A, i.e., protein A in which the Fc-binding activity was destroyed by heating protein A for 0.5 h at 110°C (1 mg ml-' of PBS, pH 7.4).…”

“…Recently, it has been shown [I, 21 that the ex vivo plasma perfusion over columns of protein A, a cell wall component isolated from most strains of Staphylococcus aureus, induces a tumoricidal response in some patients presenting with a breast adenocarcinoma and metastatic lesions. Although the Fc-binding capacity of protein A is most probably responsible for this Correspondence necrolytic response [2], the precise mechanisms involved remain poorly understood. Theoretically, two major hypotheses may be advanced: a 'column effect', i.e., the removal of antigen-antibody complexes from the plasma, leading to the appearance of cytotoxic antibodies in the processed plasma [3], or a 'leaking effect' (or both), i.e., the infusion of some agents stimulating the patients' immune response (protein A?)…”

“…The major side effects are the following: severe hypotension and tachycardia, chills, diarrhoea, pulmonary rales and temperature elevation. t Group A: plasma perfused over columns of protein A with a normal Fcbinding capacity; group B: plasma perfused over columns of 'denatured' protein A, i.e., protein A in which the Fc-binding capacity was destroyed[2].$ The differences between (b) and (a), (c) and (a), (c) and (b) are statistically significant (P < 0.01).…”

Staphylococcus Aureus Protein A Immunoadsorption: The Rationale for Systemic Protein A Immunotherapy

“…Kinet [5] has shown that the anti-n eoplastic activ ity of S PA colum ns for hum an breast adenocarcinoma is lost when SPA is chemically treated to destroy its ability to bind antibo dy. Das and Langone [21] have shown that the anti-n eoplastic activ ity for system ic SP A therapy in m ice is also dependent on S PA' s IBF activit y.…”