1035P - A new IL-6 inducing mechanism in cancer with new therapeutic possibilities

Background

To investigate new mechanisms for regulation of pathological IL-6 production.

Methods

Interleukin-6 synthesis was studied in PBMC cultures, either spontaneous in autologous cultures or stimulated by serum factors or specific peptides. Immunoregulatory albumin neo-structures were identified using 2D-gel electrophoresis and MALDI-TOF-MS. The neo-structures in serum or culture supernatants were determined by ELISA.

Results

PBMC in autologous cultures from cancer patients produce large amounts of IL-6, even in early-stage disease. Proteolytic degradation of albumin generates an IL-6 inducing neo-structure, P935, found in tumours, serum and urine. This neo-structure is immunogenic and elicits autoantibodies, resulting in immune complexes. The free neo-structure, identified by “Artificial Cell Surface Chromatography”, induces IL-6 by healthy PBMC. Such IL-6 production is inhibited by specific rabbit antibodies or by specific autoantibodies. The serum concentration of this IL-6 inducing factor, IL-6IF, is significantly higher in advanced cancer stages and is significantly correlated to the over-all survival of the patients.

Conclusions

A new mechanism for induction of IL-6 synthesis is presented. Based on this mechanism the pathological IL-6 production related to an enhanced proteolytic activity can be diagnosed and selectively inhibited by specific antibodies. Thus, the neo-structures, inducing pathological IL-6 production, associated with a reduced survival of cancer patients can be selectively removed by therapeutic administration of specific antibodies, leaving the function of IL-6 needed for the normal activity of the immune system intact.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Swedish State under the LUA/ALF agreement (ALFGBG-966007) and the Swedish Cancer Society (CAN 22 2370). Health Research Council in the South East of Sweden. Canimguide Therapeutics AB, Therim Diagnostica AB, Sweden.

Disclosure

L. Håkansson: Other, Personal, Ownership Interest: Therim Diagnostica AB. A. Hakansson: Financial Interests, Personal, Stocks/Shares: Therim Diagnostica AB. All other authors have declared no conflicts of interest.