Nature publication reports first-in-human trial for a personalized cancer immunotherapy

20.12.2018 Nature publication reports first-in-human trial for a personalized cancer immunotherapy

Clinical study demonstrates proof-of-concept for active personalized immunotherapy approach in a pioneering multi-center, multi-national study to treat brain cancer

This study is a blueprint for Immatics’ highly personalized ACTolog® adoptive cell therapy trial currently treating patients at MD Anderson Cancer Center

The prospect of an actively personalized approach to the treatment of cancer has moved a step closer with the recent publication in Nature of data from the phase 1 study GAPVAC-101, testing a novel therapeutic concept tailored to specific characteristics of patients’ individual tumors and immune systems. For the first time, the feasibility of such a highly personalized form of immunotherapy has been exemplified in a multi-center, multi-national clinical setting.

To date, glioblastoma, an aggressive form of brain cancer with poor prognosis, and other tumor types have not sufficiently benefited from recent breakthroughs with checkpoint inhibitors due to lack of high mutational load which is thought to be essential for the mode of action of this therapeutic class. Indeed, many tumor types are characterized by a low mutational load and thus only few neoantigens are targetable by the immune system. Such cancers exhibit a high unmet medical need and require additional therapeutic strategies tailored to the features of the patient’s individual tumor and appreciating the entire breadth of the cancer target repertoire.

The Glioma Actively Personalized Vaccine Consortium (GAPVAC) approach is a highly personalized method being progressed through the GAPVAC-101 first-in-human clinical trial by a European Union-funded consortium, led by Immatics Biotechnologies GmbH (Tuebingen, Germany) and BioNTech AG (Mainz, Germany).

Fifteen newly diagnosed glioblastoma patients treated at six European centers received two immunotherapies in succession; APVAC1 targeted at non-mutated antigens, followed by APVAC2 preferentially targeted at neo-antigens. Immunotherapy compositions were personalized for each patient based on analysis of the transcriptome, immunopeptidome and mutanome of the individuals’ tumors and, for APVAC1, also based on the capability of each patient to mount an immune response. Both immunotherapy types displayed favorable safety and immunogenicity. Non-mutated APVAC1 antigens induced sustained central memory CD8+ T-cell responses, whilst APVAC2 induced T helper cell type 1 (TH1) CD4+ as well as CD8+ T-cell responses against predicted neo-epitopes.

The GAPVAC-101 trial served as a blueprint for the ACTolog® IMA101-101 trial sponsored by Immatics. ACTolog® is the first adoptive cell therapy trial applying the concept of active personalization.

Dr. Harpreet Singh, Chief Scientific Officer of Immatics and President & CEO of Immatics US, said: “We are at a very exciting stage in the evolution of tailor-made cancer treatments based on the diseases of individual cancer patients. The ability to exploit the full repertoire of tumor antigens, including non-mutated and neoantigens, may offer more effective immunotherapies, especially for tumors with low mutational load. And there is more to come. The next step is to translate the concept of active personalization, successfully demonstrated in this study, into adoptive cell therapies ‒ which we have achieved with the ACTolog® IMA101 clinical trial Immatics is currently running at MD Anderson Cancer Center.”

Prof. Hans-Georg Rammensee, Head of the Department of Immunology at the University of Tuebingen, Germany, and Co-Founder of Immatics added: “I am very pleased to see that the concept of active personalization proposed by us more than a decade ago has been applied for the treatment of glioblastoma patients. GAPVAC constitutes the first clinical trial using a combination of personalized mass spectrometry, next-generation sequencing, mRNA microarray, immune repertoire analysis and peptide GMP manufacturing for every patient and delivering these complex logistics in a multi-center multi-national clinical trial.”

The approach of personalization of immunotherapies was first proposed by Prof. Hans-Georg Rammensee in 2000. His department was also responsible for the APVAC “on-demand” GMP manufacturing, led by Prof. Stefan Stevanovic, in the GAPVAC trial. The University of Tuebingen also served as one of the six European clinical trial centers treating glioblastoma patients.

Public reference:
Hilf et al., Actively personalized vaccination trial for newly diagnosed glioblastoma, Nature 2018 Advance online publication date: 19th December, 2018 (DOI: 10.1038/s41586-018-0810-y)


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