CReST™ is a novel therapeutic recombinant live oral immunotherapy platform based on the attenuated carrier strain Salmonella typhi Ty21a, which is approved as an oral vaccine against typhoid fever. S. typhi Ty21a has an excellent safety profile with more than 250 million doses already applied. The CReST™ Platform has been genetically modified to express a fusion protein of tumor-specific antigen (TSA) and cholera toxin B (CtxB) in order to induce a specific cellular immune response specifically directed towards cancer cells expressing the TSA and to stimulate innate components of the immune system.
Secretion of tumor-specific antigen (TSA) fused to the non-toxic immunostimulatory beta-subunit of cholera toxin B (CtxB) through the recombinant Escherichia coli hemolysin secretion system by the attenuated Salmonella typhi Ty21a carrier strain.
|Carrier S. typhi Ty21a||- Oral application
- Safely applied in millions of individuals (since 1980's)
- Low cost of goods / easy manufacture
- Induction of innate immunity
|Fusion Protein (tumor-specific antigen + CtxB) enables "cross presentation"||- Recombinantly produced tumor-specific antigen (TSA) → induction of TSA specific CD8 T-cell immune response
- CtxB fusion → mucosal adjuvant loads TSA on MHC class I pathway in macrophage
|E. Coli secretion system||- Active secretion of fusion protein enhances CD8 T-cell induction|
Publications & Presentations
J Fensterle, B Bergmann, P Schmidt, Michael Teifel, J Engel, T Rudel, W Goebel and UR Rapp (2012). Pre-Clinical Proof of Concept and Characterization of AEZS-120, a Therapeutic Oral Prostate Cancer Vaccine Candidate Based on Live Recombinant Attenuated Salmonella. 32nd Cong. Société Internationale d’Urologie, Fukuoka, Japan.
J Fensterle, B Bergmann, CLRP Yone, C Hotz, SR Meyer, S Spreng, W Goebel, UR Rapp and I Gentschev (2008). Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B. Cancer Gene Therapy, 15(2), 85-93.