Geert C Mudde
Title: Targeted vaccination and intrinsic adjuvant function: next generation checkpoint control of tumor specific B and T cells
Biography
Biography: Geert C Mudde
Abstract
OncoQR develops therapeutic cancer vaccines based on the S-TIR™ technology platform. Vaccines from this platform are
(non-)human specific and able to induce strong polyclonal B cell and T cell immune responses against tumour associated
(auto-)antigens. Two prototype vaccines, TYG100 and OQR200 resp., have reached in vivo proof of concept in non-human
primates (NHP). S-TIR™ vaccines consist of 2 modules, the disease specific module, “immunogen” and the generic module,
“warhead”, which directs the vaccines to CD32 on antigen presenting cells, especially pDCs and B cells and optimally activates
these cells1. The immunogen of TYG100 is G17, a growth factor for pancreatic cancer cells2 The immunogen of OQR200
targets and contains HER2/neu, overexpressed in ~20% of all breast cancer patients. TYG100 was tested as monotherapy and in
combination with gemcitabine. OQR200 were tested as monotherapy and in combination with TYG100 in a cross over study.
Four immunizations were given 2-3 weeks apart antibody titres were measured on a weekly basis. Under normal conditions no
clinically relevant immune responses can be induced against autoantigens. However, in combination with the warhead, thanks
to intrinsic check point control, all treated NHP (n=44) generated very strong and rapid dose dependent auto-antigen specific
antibody (IgG and IgA) and T cell responses. Two weeks after the 2nd immunization all animals were seroconverted. Despite
very high antibody titres no side effects were observed. Animals, sequentially treated with OQR200, TYG100 and OQR200
showed that the induced responses were 100% vaccine specific, resulting in animals with very high antibody titres against
2 different autoantigens at the same time. All responses are reversible and can be boosted. S-TIR™ vaccines do not induce
autoimmune disease and are tumour specific while optimally mobilizing both arms of the immune system. The immune
response can be fine-tuned on a patient to patient basis.