SUMMIT SIGNED

Project "SUMMIT" data sheet

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 Project 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.