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BioWin: driving cancer immunotherapy in Wallonia

Since its inception in 2006, BioWin, the health competitiveness cluster of Wallonia, Belgium, has become the point of reference for any stakeholders in the fields of biopharma and medical technology—companies, investors, research institutions, universities, and government—that are interested in partnering within the region. With 164 members, and a system in place to address all elements of the drug development cycle, from research to marketing, through biomanufacturing, clinical trials and drug registration, BioWin is a key contributor to the dynamic innovation ecosystem and economic output of Wallonia.

Focus on cancer immunotherapy

Enlisting the help of the body’s own immune system is a leading strategy in the fight against cancer. Wallonia has a high concentration of top-level researchers in immunology, oncology, and the combined translational field of cancer immunotherapy at centers such as the Ludwig Institute of Cancer Research (LICR), the de Duve Institute (DDI) at Université Catholique de Louvain, and the Institute of Medical Immunology (IMI). Against this backdrop, and given the collaborative environment fostered by BioWin, several startup companies in cancer immunotherapy have entered the scene. Here, we highlight four of these companies:

Celyad: developing a universal CAR-T therapy

Celyad is developing next-generation, genetically engineered autologous T cells expressing chimeric antigen receptors (CARs) that bind to cancer-specific antigens. Classical CAR-T cells typically only recognize one tumor antigen, which limits their use to one type of cancer.

Celyad is developing an alternative approach, dubbed CAR-T NKR-2 cells. The CAR-T NKR-2 technology consists of T cells engineered to express an artificial receptor derived from a natural receptor expressed in natural killer (NK) cells that interacts not with a single cancer antigen but with eight different ligands produced by tumor cells in response to stress. Because these ligands are expressed in many types of tumors, CAR-T NKR-2 cells could be potentially useful in up to 80% of cancer types.

Preclinical studies have shown that CAR-T NKR-2 cells not only target tumor cells, but also target ligand-expressing blood vessels that feed the tumor, and inhibitory cells that help tumors to evade the immune system within the tumor microenvironment. In addition, CAR-T NKR-2 cells trigger the generation of long-term cell memory against targeted tumors— an effect that is reminiscent of traditional vaccination—following the induction of the host adaptive immune response.

iTeos: targeting the immune tumor microenvironment to optimize patient outcomes

iTeos, a spin-off of LICR and DDI, is developing a proprietary drug pipeline targeting the tumor microenvironment in inflamed ‘hot’ tumors and non-inflamed ‘cold’ tumors. Specifically, the company is harnessing its phenotypic screening platform to develop antibodies and small molecules that modulate the immune response in two ways: through the inhibition of immune suppression in hot tumors and through the stimulation of antitumor immunity in cold malignancies.

The lead compounds of iTeos are inhibitors targeting indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2), two enzymes that are involved in tumor immune suppression. These programs are partnered with Pfizer, and one IDO1 inhibitor has already entered a phase 1 clinical trial in brain cancer.

Other early-stage programs of iTeos include small molecules and biologics aimed at increasing the immune response to hot and cold tumors that do not respond to existing immunotherapies.

The company is building a portfolio of strategic partnerships around its discovery platform and pipeline, including collaborations with Adimab, Johns Hopkins, and Cristal Therapeutics.

PDC*line Pharma: developing versatile, off-the-shelf therapeutic cancer vaccines

PDC*line Pharma is developing a line of plasmacytoid dendritic cell (PDC)-based cancer vaccines derived from a proprietary allogeneic human PDC line (Fig. 1). Compared with autologous dendritic cells, these PDCs display strongly enhanced antigen-presenting cell abilities.

PDCs are easy to expand to large quantities in bioreactors, and can express any combination of synthetic peptides derived from tumor-specific antigens. The off-the-shelf product can be stored frozen for years and, once injected to patients, it induces a potent and targeted cytotoxic T cell response against tumor cells, including neoantigens.

Lead products include PDC*mel, a vaccine for advanced melanoma that is currently in a first-in-human phase 1 clinical trial, and PDC*lung, a preclinical vaccine candidate for lung cancer.

ImmunXperts: customized support for immunotherapy developments

ImmunXperts is an R&D in vitro testing organization offering comprehensive and customized predictive and functional assessment solutions for companies that are developing therapeutics, specifically cancer immunotherapies.

Through its global network of immunology experts and partners, ImmunXperts has access to the best advice and infrastructure needed to offer support for early-stage candidate screening and selection. Using in vitro assays to measure and assess the effect of a drug candidate on immune cells, the more promising and less risk-bearing drug candidates are selected, drastically increasing the chances of these drug candidates of passing later in vivo tests and clinical trials.

ImmunXperts designs test combinations that are specifically tailored to a client’s drug in development, and is continuously updating its offerings to include the latest advances in immunogenicity assessment. Ultimately, ImmunXperts aims to serve as a flexible and rapidly adjusting development arm to its partnering clients.

Figure 1: Cancer immunotherapy—a key driver of innovation in Wallonia. Shown here, cytotoxic T cells (gray) activated by a plasmacytoid dendritic cell (PDC)-based cancer vaccine (blue) attacking a tumor cell (red). (Photo courtesy of PDC*line Pharma)

Driving global partnerships

At the heart of BioWin’s mission to promote innovation in cancer immunotherapy and the life sciences lies a philosophy of open collaboration that illustrates the dynamism of a region not only open to technological partnerships but also offering a vibrant ecosystem to support those partners—a region that equally invests in, and supports the growth of, scientific excellence and entrepreneurial leadership.


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