The PB013 project’s primary goal is to develop new CAR molecules, ready for clinical trials in humans. The engineered CARs, based on a new set of targets and generated antibodies, will be affinity-optimized and validated in pre-clinical settings using well-established in vitro and in vivo models. Selected CAR(s) will then be manufactured as GMP-grade RNA for a first-in-human study. The final product of this project will be one or more alternative CARs, to be used in patients as a new therapy for leukemia and lymphoma.
Cancer is a leading cause of death worldwide, causing more than 100 000 deaths in Poland and Norway in the year 2018, according to the IARC. Research and medical communities in both countries are fully aware that cancer has considerable social consequences – not only affecting families, but also having macroeconomic impacts.
Specific recognition of cancer-related molecules by the human immune system makes it an extremely precise and highly suitable tool for personalizing anticancer treatments. Numerous reports documenting the resistance of patients to currently registered targeted therapies, have stimulated intensive research efforts aimed at identifying novel therapeutic schemes. Several alternative treatment strategies are currently being developed, which plan to employ targeted therapies or immunotherapies in parallel, to simultaneously target resistance mechanisms with the hope that a particular combination will limit escape mechanisms of cancer cells. The ALTERCAR project proposes a strategy to specifically recognize and eliminate tumor cells resistant to the current treatment methods. The hypothesis behind this approach is that resistance mechanisms limiting these therapies could be targeted through cell-based immunotherapies: resistant tumor cells expressing specific antigens will be effectively targeted and eliminated using CAR-based approaches.
In the first stage of the project, we will employ a combined bioinformatic-transcriptomic-proteomic approach to identify new targets for CAR T cells using established tumor cell lines. Selected antigens will be validated in primary cells isolated from acute lymphoblastic leukemia and lymphoma patients refractory to standard-of-care treatment. The selected antigens will then be used to design a panel of CAR constructs, which will be further validated in pre-clinical settings using well-established in vitro and in vivo models. In the final stage, selected CAR(s) will be manufactured as GMP-grade RNA for a first-in-human study. The final product of PB013 will be one or more alternative CARs, to be used in the treatment of patients with B cell malignancies refractory to all treatment options, or in patients who relapse after previous therapies.
PURE BIOLOGICS’ ROLE
Pure Biologics’ role in the PB013 project will be to participate in the identification of targets and later their production, but mainly in discovering new antibodies towards those targets. The company will employ its phage display libraries and platforms to identify new binders, which will be subsequently optimized and fully profiled, including binding characterization, epitope evaluation and assessments of developability properties. These new antibodies will then be transferred to CAR molecules and studied as recognition and initiator molecules in CAR-enabled T cells.
The first phases of the project are underway to identify and evaluate new potential molecular targets. In parallel new antibodies against these targets are being generated.
PROJECT DATA SHEET
Title: Development of alternative CAR constructs targeted against refractory B-cell malignancies
Program: Programme ‘Applied Research’ under the POLNOR 2019 call of EEA and Norway Grants. Fundusze Norweskie i Fundusze Europejskiego Obszaru Gospodarczego (EOG).
Project value: PLN 412 625,00 (the entire consortium: PLN 6 655 250,67)
Contribution of European Funds: PLN 330 100,00 (the entire consortium: PLN 6 572 725,00)
Start: 1st January 2021
End: 31st December 2023
Consortium members: Oslo University Hospital (Norway), Warsaw Medical University (Poland), Pure Biologics S.A.