Oncology

Prostate cancer and melanoma

Preclinical development

Cellular proteins expressed by oncogenes have been recognized as a major cause of tumor development. Raf proteins belong to the central oncoproteins involved in cancer formation. Based on these proteins, unique therapeutic strategies, new predictive animal models and innovative products have been generated to efficiently combat cancer. These consist of virulence attenuated, gene modified bacteria which express oncoproteins or enzymes. Such bacteria can be used for vaccination, as well as tumor targeting and delivery of antitumoral compounds towards the tumor tissues. The bacterial carrier system represents a platform technology which can be combined with a wide range of antigens or enzymes.

This new vaccine approach therefore exploits the ability of bacteria to induce potent immune responses. Intracellular bacteria can be delivered orally and typically target cells of the immune system which initiate systemic immune responses. The activation is further enhanced by several bacterial components which act as intrinsic adjuvants as well as the proprietary expression system. These factors make bacterial carriers less sensitive to tolerance or suppressive immunity, which often hampers the efficacy of conventional vaccines in cancer. In addition, the immunogenicity of the vaccine will further be enhanced by the capacity of bacteria to colonize tumor tissues.
The image illustrates the theory behind bacterial tumortherapy. There are three proposed pathways by which the bacteria can induce antitumor immunity:

• Reprogramming of tumor milieu by bacterial components (A)
• Induction of tumor specific immunity by bacteria carrying tumor antigen (B)
• Pro-Drug activation by bacterially delivered enzymes (C)

All sequences of events lead to death or retardation of growth in cancer cells

The preclinical proof of this principle has already been shown in a transgenic animal model and is supported by several patent applications

The use of bacterial carriers for therapeutic vaccination against tumors and the concept of bacterial tumor targeting will be further developed with the Julius-Maximilians-University including the highly recognized researchers Prof. Dr. Ulf R. Rapp and Prof. Dr. Werner Goebel. Professor Rapp, the discoverer of Raf proteins, is a known expert in the field of cell and tumor biology and Prof. Goebel is a pioneer in the field of vaccines based on recombinant bacteria.
The first expected targets for this research project would be the development of vaccines against prostate cancer and melanoma.

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