Ovarian cancer is one of the most challenging malignancies in oncology. Despite advances in diagnosis and treatment, it is still the deadliest gynaecologic cancer, claiming about . In far too many patients, the story is heartbreakingly familiar: an initial response to platinum-based chemotherapy is followed by recurrence within one or two years, leaving fewer and less effective treatment options available.
In fact, experience disease recurrence following initial treatment. Resistance to existing therapies is the major cause of death. Immunotherapy, which works to turn the immune system against the tumour, has revolutionised therapy for melanoma and non-small cell lung cancer and others, but has yet to achieve a similar impact in ovarian cancer. The reason for the historic underperformance of immunotherapy in ovarian cancer likely lies in its hostile tumour microenvironment (TME), which actively suppresses anti-tumour immune responses.
But now, a new therapeutic paradigm is emerging that fuses the innate tumour-homing and infiltrating ability of stem cells with the precision and programmability of bioengineered medicine. At the forefront of this shift is a novel approach: synthetic, allogeneic induced mesenchymal stem cells (iMSCs) engineered not just to reach tumours, but to reprogramme the tumour microenvironment itself 鈥� turning sites of immune suppression into hubs of immune activation.
Why ovarian cancer has been so hard to crack
To appreciate the potential of iMSC-based therapies, first, it鈥檚 important to understand why ovarian cancer is so challenging. Most patients are diagnosed at an advanced stage 鈥� Stage 3 or 4 鈥� at which point the disease has already spread deep throughout the abdominal cavity. The current standard of care, typically involving a combination of aggressive surgery followed by a combination chemotherapy regimen, offers only temporary control. Recurrence is not the exception, but the norm.
Targeted therapies, such as PARP inhibitors and anti-angiogenic agents, have expanded treatment options for some patients, but their benefits are often limited and short-lived. Immune checkpoint inhibitors, which have transformed the management of other solid tumour malignancies, have shown only modest success with ovarian cancer due to the immunosuppressive TME. Ovarian tumours are typically immunologically 鈥榗old鈥�. In other words, they have few infiltrating T cells and actively suppress immune activity through processes such as TGF-beta secretion and recruitment of immunosuppressive tumour-associated macrophages (TAMs) and regulatory T cells.
Furthermore, many therapies fail to reach the tumour’s core. Ovarian tumours are notorious for their dense extracellular matrix and fibrotic stroma that create a physical barrier to drug delivery. This two-pronged challenge of immune evasion and poor penetrability has kept ovarian cancer on the wrong side of survival rates for decades, despite persistent effort.
US Tariffs are shifting - will you react or anticipate?
Don鈥檛 let policy changes catch you off guard. Stay proactive with real-time data and expert analysis.
By GlobalDataThe rise 鈥� and fall 鈥� of early MSC therapies
MSCs have been of particular interest in regenerative medicine because of their natural ability to home in on sites of inflammation, tissue damage, and notably, tumours. This natural migration makes MSCs uniquely suited for delivering therapeutic cargo directly into the TME, where traditional therapies often struggle to reach.
Early clinical efforts with MSCs were hindered by significant limitations. Autologous MSCs 鈥� derived from a patient鈥檚 own tissue 鈥� were slow to manufacture, costly, and inconsistent in quality. Allogeneic MSCs 鈥� derived from one or more donors 鈥� offered improved scalability and reduced time-to-treatment but often triggered immune responses or failed to persist long enough in vivo to be therapeutically effective. Both approaches lacked the potency and batch-to-batch consistency needed for clinical success.
As such, despite early promise, MSC-based treatments struggled to deliver on their potential 鈥� until now. Recent breakthroughs in cell engineering and synthetic biology have enabled improved MSC treatments.
A new-generation platform: synthetic allogeneic iMSCs
Recent advances in stem cell engineering have radically improved upon the MSC paradigm. Synthetic, allogeneic iMSCs represent a new-generation cell therapy that overcomes the critical limitations of past approaches.
iMSCs are derived from engineered induced pluripotent stem cells (iPSCs) 鈥� adult cells that have been reprogrammed to a stem cell-like state and engineered through the application of synthetic biology tools to maximise their function, persistence, and specificity before being differentiated into MSCs for large-scale expansion. Crucially, they are allogeneic 鈥� manufactured from a single healthy donor source and scaled to enable off-the-shelf availability with consistent, reproducible performance across batches.
Synthetic iMSCs engineered to secrete immune-stimulating cytokines like IL-7 and IL-15 can migrate into the tumour, secrete their therapeutic cargo directly into the microenvironment, and activate T cells in situ 鈥� potentially rendering 鈥榗old鈥� tumours 鈥榟ot鈥� and susceptible to immune attack.
Strong early evidence from ASCO
New preclinical data reported at the 2025 American Society of Clinical Oncology (ASCO) annual meeting highlighted the potential of iMSC-based therapies to penetrate the ovarian TME and activate robust immune responses. In one example, iMSCs engineered to express IL-7 and IL-15 drove vigorous T cell infiltration in mouse models of ovarian cancer, reducing tumour burden and improving survival. These cytokines are well established for their role in promoting T cell expansion, resisting exhaustion, and preserving cytotoxic function 鈥� all essential for long-lasting anti-tumour immunity. Interestingly, iMSCs homed selectively to tumour tissue, concentrating cytokine activity where it鈥檚 needed most and limiting systemic exposure and off-target toxicities.
Another presentation demonstrated the in vivo stability of iMSCs, solving one of the key limitations of earlier MSC platforms. In animal models, the cells persisted long enough to induce a therapeutic effect, yet did so without eliciting an intense immune rejection. Collectively, these findings suggest that synthetic iMSCs could serve as a powerful adjunct to existing ovarian cancer treatments 鈥� and potentially serve as a standalone therapeutic alternative.
A future that’s tumour-targeted and immune-activated
For decades, the conventional approach to treating ovarian cancer has been systemic: flood the body with chemotherapy or immunotherapy and hope that enough reaches the tumour to have an impact. Synthetic iMSCs disrupt this model by delivering anti-cancer agents directly to the tumour, concentrating activity where it鈥檚 needed most and minimising collateral damage to healthy tissue.
This precision-guided strategy is also highly adaptable for combination regimens. Imagine pairing iMSCs with checkpoint inhibitors or PARP inhibitors to maximise efficacy, deploying them in the maintenance setting to prevent relapse by sustained immune vigilance. As synthetic biology becomes increasingly mature, the payloads iMSCs can deliver are virtually limitless, from cytokines to gene-editing machinery, RNA therapeutics, or tumour antigens that stimulate immune memory, all with a level of control, consistency, and customisation that was previously unthinkable.
Looking ahead
The journey to revolutionising the treatment of ovarian cancer will not be easy. But the emergence of allogeneic iMSCs marks a meaningful leap forward in our ability to target hard-to-treat tumours. Rather than fighting the tumour from the outside in, these engineered cells allow us to go in and fight it from the inside out, armed with the tools to reprogramme the microenvironment and reawaken the immune system.
For patients facing relapse or resistance, this approach may offer what they previously lacked: a genuine second chance. And for the broader oncology community, it could signal a new era in which engineered cell therapies move from the forefront to the foundation of cancer care.
