Objective
Immunotherapy is expected to fundamentally change the treatment of cancer patients. Personalized vaccines eliciting
immune responses against individual cancer mutations have moved into the spotlight. We have pioneered the field and
moved ´cancer mutanome vaccines´ from a mere vision into a disruptive medical concept compatible with current
standards of drug development and health care practice. Solving key scientific and technological challenges and building
on extensive preclinical studies, we showed in a first-in-human trial potent tumor-directed immunity in every single
vaccinated patient, and clinical activity of a novel mRNA-based mutanome vaccine. Given that mutations are a hallmark
of cancer, mRNA mutanome vaccines are universal drugs the efficacy of which are unaffected by the cancer type. The
aim of this proposal is to ignite the next wave of advancement by addressing four key constraints challenging a full clinical
realization of such vaccines. We will address the scarcity of point mutations in many tumors by extending neoepitope
discovery to the full spectrum of genetic aberrations. Cancers are heterogeneous and outgrowth of clones unaccounted
for by the vaccine is an efficient escape mechanism. We will develop neoepitope prediction algorithms deciphering clonal
heterogeneity to inform rational vaccine design and countermeasures against selection of target escape variants. Tumor
cell resistance to vaccine-induced T cells due to antigen presentation defects will be addressed by developing strategies
for mobilizing the full repertoire of immune effector mechanisms, including antibodies and NK cells. T-cell exhaustion will
be tackled by vaccination protocols promoting long-lived memory responses and by combination treatments counteracting
tumor-mediated immunosuppression. Finally, we will drive the seamless clinical translation of the scientific findings by
close interdisciplinary collaboration with strong and established clinical and industrial partners.
Fields of science
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Keywords
Programme(s)
Topic(s)
Funding Scheme
ERC-ADG - Advanced GrantHost institution
55131 Mainz
Germany