Cytokines: Signalling the Immune System to Fight Back

Sarcoma is a rare and heterogeneous group of neoplasms originating from mesenchymal tissues such as bone, fat, joints, and muscle. It is primarily divided into two major categories: soft-tissue sarcoma (STS), which includes around 60 subtypes, and bone sarcoma, with the main subtypes being osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. The varied molecular and genomic mechanisms within these subtypes lead to a growing number of immunological profiles based on the tumour microenvironment. Around 20% of patients with stage III or IV sarcomas have a 5-year survival rate and 40%–60% of high-grade cases experience disease relapse, underscoring the urgent need for novel therapies to improve outcomes in advanced disease stages.

Various immunotherapies are being considered for treating sarcomas, either alone or as a combinatorial therapy with chemotherapy and/or radiotherapy. Cytokines, including interleukins (ILs), interferons (IFNs), and tumour necrosis factor (TNF), are crucial immunoregulatory proteins that promote the growth, differentiation, and activation of normal cells while maintaining physiological balance and modulating disease processes. Over nearly four decades, these molecules have been extensively studied, particularly in cancer immunotherapy. Cytokines exert their biological effects through cell membrane receptor extracellular domains and play a vital role in cellular communication between immune cells within the tumour microenvironment. Cytokine therapy targets tumour destruction through two main mechanisms: either by directly acting on tumour cells to inhibit their proliferation via apoptosis, angiogenesis suppression, and modulation of differentiation or by stimulating anti-cancer immune responses through the administration or blockade of specific cytokines that interfere with relevant signaling pathways.

Since IFN α became the first FDA-approved biotherapeutic, innovative engineering approaches have emerged globally to enhance cytokines' therapeutic potential for developing safe and effective sarcoma treatments. These trials aim to reduce immune-related toxicities associated with conventional treatments and assess their efficacy in early-stage cancers. Transforming Growth Factor (TGF-β) is being evaluated as a potential osteosarcoma treatment, highlighting its promising role in advancing cancer therapy. In the clinical translation of cytokine therapies, GMP manufacturing is essential to ensure a consistent supply of safe and effective medicines while maintaining high batch consistency during upscaling.

DDE is a turnkey biopharma equipment provider catering to the GMP manufacturing of cytokines from pilot scale to commercial development. By leveraging our scalable technologies, biopharmaceutical companies can significantly reduce production costs while strictly adhering to the regulatory requirements at each stage. DDE strives to enable biopharmaceutical manufacturers with customizable bioprocess systems that pave the way for the development and easy translation of new and affordable cytokine therapies that can improve the life expectancy in sarcoma patients. 

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Northwest Sarcoma Foundation Sarcoma Foundation of America Cancer Research UK (CRUK) J&J Medical Affairs Oncology Oncology Insights American Cancer Society Frederick National Laboratory for Cancer Research NCI Center for Cancer Research Cancer Research UK Science and Innovation CANCER CARE BEACON NCI Division of Cancer Prevention