0000000000341726
AUTHOR
Isabel Vogler
Abstract CT202: IVAC MUTANOME: Individualized vaccines for the treatment of cancer
Abstract Cancer arises from the accumulation of genomic alterations and epigenetic changes that constitute a hallmark of cancer. Owing to the molecular heterogeneity in cancer, only a minor fraction of patients profit from approved therapies. Available targeted therapies can only address alterations common to a particular type of cancer and induce transient effects due to the generation of resistant sub-clones. In contrast, the IVAC MUTANOME project aims to immunologically target multiple cancer mutations uniquely expressed in a given patient's tumor. The IVAC MUTANOME approach should be applicable to the majority of patients irrespective of the tumor entity and offers the potential to expl…
BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans
BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy to prevent coronavirus disease 2019 (COVID-19). Recently, we reported preliminary BNT162b2 safety and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 vaccine trial1. We present here antibody and T cell responses from a second, non-randomized open-label phase 1/2 trial in healthy adults, 19-55 years of age, after BNT162b2 prime/boost vaccination at 1 to 30 µg dose levels. BNT162b2 elicited strong antibody …
A shared tumor-antigen RNA-lipoplex vaccine with/without anti-PD1 in patients with checkpoint-inhibition experienced melanoma.
3136 Background: Cancer vaccines are considered unsuitable for patients with advanced tumours and have not been clinically successful. Methods: Lipo-MERIT is an ongoing phase 1/2 trial (NCT02410733) with melanoma FixVac, a liposomal RNA vaccine targeting four non-mutant shared tumour-associated antigens (TAAs) (MAGE-A3, NY-ESO-1, tyrosinase, TPTE). Patients with stage IIIB-C and IV melanoma are eligible. The trial comprises 7 dose escalation and 3 dose expansion cohorts, the latter with FixVac alone or combined with anti-PD1. Eight doses of FixVac are administered i.v. weekly/bi-weekly followed by optional continued monthly treatment. This abstract summarizes the findings of an exploratory…
Abstract CT022: IVAC® MUTANOME - A first-in-human phase I clinical trial targeting individual mutant neoantigens for the treatment of melanoma
Abstract One of the hallmarks of cancer is the inherent instability of the genome leading to multiple genomic alterations and epigenetic changes that ultimately drive carcinogenesis. These processes lead to a unique molecular profile of every given tumor and to substantial intratumoral heterogeneity of cancer tissues. Recently, a series of independent reports revealed that pre-formed neoantigen specific T-cell responses are of crucial relevance for the clinical efficacy of immune checkpoint inhibitors. However, spontaneous immune recognition of neoantigens seems to be a rare event with only less than 1% of mutations inducing a T-cell response in the tumor-bearing patient. Accordingly, only …
549 An RNA-lipoplex (RNA-LPX) vaccine demonstrates strong immunogenicity and promising clinical activity in a Phase I trial in cutaneous melanoma patients with no evidence of disease at trial inclusion
BackgroundLipo-MERIT is an ongoing, first-in-human, open-label, dose-escalation Phase I trial investigating safety, tolerability and immunogenicity of BNT111 in patients with advanced melanoma. BNT111 is an RNA-LPX vaccine targeting the melanoma tumor-associated antigens (TAAs) New York esophageal squamous cell carcinoma 1 (NY-ESO-1), tyrosinase, melanoma-associated antigen 3 (MAGE-A3), and transmembrane phosphatase with tensin homology (TPTE). A previous exploratory interim analysis showed that BNT111, alone or combined with immune checkpoint inhibition (CPI), has a favorable adverse event (AE) profile, gives rise to antigen-specific T-cell responses and induces durable objective responses…
Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer
T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit p…