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Enjoy reading! - The SMS-oncology team
Cancer stem cells (CSCs) play a key role in treatment relapse and metastasis. It is still incompletely understood what signals manipulate the 'stemness' or these cells. Researchers have now identified that tumor-associated macrophages play a key role here. Central to their results is the LSECtin / BTN3A3 axis. LSECtin is mostly known as a pathogen receptor, but it was found that tumor cells may upregulate this protein on tumor-associated macrophages (TAMs). These TAMs were next found to promote tumor initiation and tumor growth in cancer models, especially when highly expressing BTN3A3. Direct contact between the CSCs and TAMs was required, and the interplay between these cell types was actively propagated by the tumor. Interestingly, the researchers found that targeting BTN3A3 with an antibody synergized with chemotherapy. As such, the dependence on tumors on this mechanism might have been translated into novel therapies.Nature Cell Research (Image source: http://sciencemag.org, Fox et al.)
Researchers at Massachusetts General Hospital have developed a new animal model with which they can accurately study human tumors outside patients. In Cell, they describe a mutant zebrafish strain in which both solid and blood human tumors can be engrafted. The tumors were successfully maintained for over 28 days and progressed to structures similar to what is seen in humans. As the zebrafish are optically clear, the researchers were able to assess the tumors at an unprecedented level in a living animal. The capabilities of the model were illustrated by the authors studying the effect of olaparib and temozolomide combination therapy on rhabdomyosarcoma. Though both chemotherapies alone prove ineffective against this tumor type, these drugs collectively inhibited tumor growth. As such, this model might provide a platform to assess novel cancer therapies on human tumors before moving to clinic, reducing costs, time and patient burden involved. Cell (Image source: Yan et al.)
Kiadis Pharma acquires CytoSen: The Dutch biotech company Kiadis Pharma has acquired CytoSen Therapeutics. CytoSen stock owners received 1,94M Kiadis stocks as an upfront payment (€17,8M at current stock price), with 5,82M stocks to be transferred based on milestones. Both companies develop immunotherapies aimed to improve blood cancer patients’ survival after and efficacy of hematopoietic stem cell transplantation (HSCT). Further, both companies use family members’ cells as the foundation of their immunotherapy, whereas Kiadis did so with T cells, and CytoSen used NK cells. With this merge, these two similar approaches may jointly revamp HSCT treatment.
Advancing immunotherapy using artificial intelligence: A research collaboration has been established between OSE Immunotherapeutics and Léon Bérard Cancer Center (CLB). These French companies together will seek to identify immunotherapy targets using artificial intelligence (AI). Within the field of immunotherapy, the companies will initially focus on identifying the underlying factors causative for PD-1/PD-L1 immune checkpoint inhibitor resistance of cancers.
Bristol-Myers Squibb acquires Celgene: The $74B deal that has been in the news since January was fully settled last month. With this deal, Bristol strengthens its portfolio in cancer drugs, specifically in immuno-oncology. Celgene has an expansive oncology pipeline, including CAR-T therapies that might revolutionize cancer treatment. Through this acquisition, these companies together seek to accelerate the development of this pipeline.
Hookipa raises $84M: During an IPO, Hookipa has sold 6 million shares at $14 each. As a biotech company that focuses on immunotherapy, Hookipa aims to induce immune responses through arenavirus vectors, rather than the current practice of lab culturing allogeneic cells. With this successful IPO on April 18, investors showed confidence in Hookipa’s pipeline and stock prices have stayed stable since.
The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:
- Libtayo (cempiblimab, Regeneron) for the treatment of advanced cutaneous squamous cell carcinoma (CSCC). Even though an increasing amount of PD-1 inhibitors has been approved in several tumor indications, Libtayo is the first PD1i to be approved in CSCC, the second most common form of skin cancer. Moreover, Libtayo is the first and only treatment option available for certain patients with advanced CSCC. Libtayo was evaluated by the FDA under Priority Review, and back in 2017, was granted Breakthrough Therapy Designation status for advanced CSCC.
- Talzenna (talazonparib, Pfizer) for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer. The EMA approval of this PARP inhibitor follows the recent approval from the FDA for the same indication last year. Critics argued that it might be challenging for Talzenna to fit in the breast cancer market.
The CHMP extended the therapeutic indication for:
- Lynparza (olaparib, AstraZeneca) as monotherapy for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer. The PARP inhibitor was earlier approved by the EMA for adult patients with platinum-sensitive relapsed variants of this tumor type, as well as HER2 negative locally advanced or metastatic breast cancer.
The FDA granted approval for:
- Balversa (erdafitinib, Janssen Oncology) was given accelerated approval for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) that had at least one susceptible FGFR3 gene mutation or FGFR gene fusion. Balversa is the first FGFR kinase inhibitor approved by the FDA.
One draft guideline from the FDA has been published:
- Bispecific Antibody Development Programs Guidance for Industry: This guidance provides recommendations to assist industry and other parties involved in the development of bispecific antibodies. Bispecific antibodies target multiple epitopes simultaneously and have possible advantages over drug mixtures, for example by delivering a specific effector cell to a specific target cell. The guidance includes general considerations and recommendations for bispecific antibody development programs, as well as regulatory, quality, nonclinical, and clinical considerations in this context. Although the guidance is specific to bispecific antibodies, the principles may also be applicable to the development of other types of bispecific protein products, such as TCR conjugated to antibody fragments (ImmTAC). With the increasing advances in bispecific antibody development, this guidance might help companies pushing this frontier in cancer treatment.