City of Hope and Collaborators Report Promising Phase 1 Results for SER-155, a 16-Strain Live Biotherapeutic Designed to Prevent Bloodstream Infections in Stem Cell Transplant Patients
City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the United States, has announced promising findings from a first-in-human clinical investigation of an innovative microbiome-based therapy designed to prevent serious bloodstream infections in patients undergoing donor stem cell transplantation for blood cancers. Researchers from City of Hope, Memorial Sloan Kettering Cancer Center, and Seres Therapeutics collaborated to evaluate SER-155, an investigational live biotherapeutic product containing 16 carefully selected beneficial bacterial strains intended to restore the gut microbiome and protect vulnerable patients against harmful pathogens.
The findings from the multicenter Phase 1 clinical trial demonstrated that SER-155 was well tolerated, with no treatment-related side effects reported. Patients who received the investigational therapy also experienced fewer bloodstream infections and lower levels of harmful bacteria associated with infectious complications.
The study, sponsored by Seres Therapeutics, has been published in the peer-reviewed journal Nature Medicine. The publication, titled “A First-in-Human Phase 1b Trial of SER-155, an Investigational, Cultivated, Live Biotherapeutic Product, in Adult Allogeneic Hematopoietic Cell Transplantation Recipients,” provides early clinical evidence supporting the potential use of scientifically designed live biotherapeutic products in patients with severely weakened immune systems.
The research represents an important development in microbiome-based medicine, particularly for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT), a treatment frequently used for leukemia and other blood cancers. Although donor stem cell transplantation can offer a potentially curative treatment option, the procedure significantly compromises the immune system and leaves patients vulnerable to serious infections during recovery.
Bloodstream infections are among the most concerning complications in this population because they can progress to sepsis, a potentially life-threatening condition. Current preventive approaches largely rely on antibiotics, which can also disrupt beneficial gut bacteria and contribute to the imbalance of the microbiome.
SER-155 is designed to address this underlying problem by introducing a defined combination of beneficial bacteria with specific biological functions intended to limit the growth of harmful pathogens, support immune regulation, and help restore a healthier microbial environment.
Marcel van den Brink, M.D., Ph.D., Chief Physician Executive at City of Hope and the Morgan and Helen Chu Presidential Chair of City of Hope National Medical Center, served as the senior author of the study. He described the findings as a significant milestone for microbiome-based therapeutic development.
“This is a landmark study for the field,” Dr. van den Brink said. “The immediate result is fewer bloodstream infections, but the larger significance is what it tells us about the future of medicine. For the first time, we’ve shown that it’s possible to design a consortium of beneficial bacteria with a specific clinical purpose and to safely deliver it to highly vulnerable patients. That opens the door to an entirely new class of therapies.”
Addressing Microbiome Disruption in Cancer Treatment
The human microbiome consists of trillions of bacteria and other microorganisms that live in and on the body. These microbial communities play important roles in digestion, metabolism, immune system regulation, and protection against harmful pathogens.
In recent years, the microbiome has become an increasingly important area of cancer research. Scientists are investigating how the composition and activity of gut bacteria can influence treatment responses, recovery following cancer therapy, immune function, and the development of treatment-related complications.
Changes in the microbiome can be particularly significant among patients receiving intensive cancer treatments, including chemotherapy, radiation therapy, and stem cell transplantation.
These treatments can damage the gastrointestinal system, suppress immune function, and disrupt the balance of beneficial and harmful microorganisms. When protective bacteria are depleted, harmful pathogens may gain access to nutrients and ecological space that would otherwise be occupied by beneficial microbial populations.
This disruption can increase the risk of infections, including bloodstream infections that may require intensive medical intervention.
Patients undergoing allogeneic stem cell transplantation are especially vulnerable because the procedure involves replacing the patient’s diseased or damaged blood-forming cells with healthy donor stem cells. The conditioning treatments administered before transplantation, together with the period required for immune recovery, can leave patients with limited protection against infections.
Although antibiotics are commonly used to prevent or treat infections during this period, they can also eliminate beneficial bacterial populations and further disrupt the microbiome.
According to the researchers, existing preventive approaches do not specifically address the underlying microbial imbalance that contributes to infection susceptibility.
SER-155 is being developed to address this unmet need by introducing selected beneficial bacteria designed to re-establish protective microbial functions and reduce the ability of harmful pathogens to colonize the gastrointestinal environment.
Limitations of Conventional Microbiome Restoration Approaches
Fecal microbiota transplantation has previously been used to restore healthy bacterial communities in patients experiencing severe microbiome disruption, particularly those with recurrent Clostridioides difficile infection.
This approach involves transferring microbial material from a healthy donor to a recipient to help restore a more balanced intestinal environment.
However, conventional fecal transplantation involves introducing a complex mixture of microorganisms. The exact bacterial composition can vary between donors, making it difficult to consistently identify the specific organisms and biological functions being transferred.
This variability can create additional safety concerns for patients with severely compromised immune systems, including individuals undergoing cancer treatment and stem cell transplantation.
For these patients, introducing an uncontrolled mixture of microorganisms may carry potential risks because certain bacteria could cause infections or produce undesirable biological effects.
SER-155 takes a different approach by using a carefully defined bacterial consortium containing 16 selected strains. Rather than introducing a broad and variable microbial mixture, researchers selected individual bacterial strains based on their potential to perform specific functions associated with infection prevention and microbiome restoration.
The objective is to develop a standardized, controlled, and targeted therapeutic product that can be administered to vulnerable patients while minimizing the uncertainty associated with less precisely defined microbiome-based approaches.
SER-155: A Targeted Therapy Containing 16 Beneficial Bacterial Strains
SER-155 is an investigational live biotherapeutic product developed using 16 carefully selected bacterial strains. Each strain was selected based on its potential contribution to restoring microbiome function and protecting against harmful pathogens.
The therapeutic approach focuses on several biological mechanisms.
Competition for nutrients and ecological space: Certain beneficial bacteria can consume nutrients required by harmful microorganisms. By occupying available resources, these bacteria may limit the ability of disease-causing pathogens to grow and establish themselves within the gastrointestinal tract.
Production of pathogen-inhibiting compounds: Some bacterial strains can produce substances that interfere with the growth or survival of harmful microorganisms. These biological compounds may provide an additional protective mechanism against infection-associated pathogens.
Immune system regulation: The selected bacterial strains are also intended to influence immune responses and support the restoration of a healthier relationship between the gut microbiome and the host immune system.
By combining bacteria with complementary biological functions, SER-155 is designed to create a more protective microbial environment.
The approach represents a shift from simply replacing missing bacteria toward engineering a defined microbial community for specific therapeutic objectives.
Dr. van den Brink explained the distinction between conventional microbiome restoration and the targeted strategy used in SER-155.
“Instead of giving patients a broad mix of bacteria, we selected specific strains for specific jobs and put them into a single pill,” he said. “That level of precision is what makes this approach fundamentally different from simply trying to replenish the microbiome. We’re moving from observing the microbiome to engineering it for specific therapeutic outcomes.”
This strategy could have broader implications for developing microbiome-based medicines for patients whose microbiomes are disrupted by intensive medical treatments.
Phase 1 Clinical Trial Evaluates Safety and Microbiome Restoration
The multicenter Phase 1 clinical trial investigated the safety, tolerability, and biological activity of SER-155 in adult patients undergoing allogeneic hematopoietic cell transplantation.
A major consideration in the study was whether administering live bacteria to severely immunocompromised patients could be performed safely.
Patients undergoing stem cell transplantation are particularly susceptible to infections because their immune systems are suppressed during treatment and require time to recover following transplantation.
Consequently, introducing live microorganisms into this population requires careful evaluation of potential infection risks and other treatment-related complications.
As part of the clinical trial protocol, researchers first administered antibiotics to patients to reduce the existing microbial populations in their gastrointestinal systems. This process was intended to create an environment in which the beneficial bacterial strains contained in SER-155 could establish themselves more effectively.
Following antibiotic treatment, patients received SER-155 in pill form.
The treatment was administered before transplantation and repeated at least once after the transplant procedure. The additional treatment was important because many patients receive antibiotics during the transplantation and recovery period to prevent or manage infections.
These antibiotics can disrupt newly established microbial populations, making repeated administration of the investigational therapy relevant to the study’s microbiome-restoration strategy.
The clinical findings demonstrated that SER-155 was well tolerated, with no treatment-related side effects reported. Researchers also did not identify complications involving infections attributed to the administration of the live biotherapeutic product.
Dr. van den Brink described the safety findings as encouraging.
“The safety profile was excellent — we didn’t see any complications with infections,” he said.
The results provide early evidence that a carefully selected bacterial consortium can be administered to patients with severely compromised immune systems without identifying treatment-related infectious complications in the study.
However, larger clinical trials will be necessary to further establish the safety profile and determine the appropriate role of SER-155 in clinical practice.
Beneficial Bacteria Successfully Establish in the Microbiome
In addition to evaluating safety, researchers investigated whether the bacterial strains administered through SER-155 could successfully establish themselves within the patients’ microbiomes.
The findings indicated that the beneficial bacteria successfully colonized the microbiome, with particularly strong establishment observed following the second course of treatment.
This observation supports the scientific rationale behind the treatment schedule, which includes administration before transplantation and repeated dosing following the procedure.
The ability of the selected bacteria to establish themselves is an important component of the therapy’s intended mechanism.
For a live biotherapeutic product to provide sustained biological benefits, the administered microorganisms must be capable of surviving within the gastrointestinal environment and performing their intended functions.
The successful establishment of beneficial bacterial populations suggests that SER-155 may help restore microbial functions that are disrupted by intensive cancer treatments and antibiotic exposure.
Although the Phase 1 study was not primarily designed to evaluate clinical efficacy, the researchers also reported encouraging early findings involving infection-related outcomes.
Patients who received SER-155 had lower levels of harmful pathogens associated with bloodstream infections and experienced a significantly lower risk of bloodstream infections.
These observations suggest that microbiome restoration may offer a complementary strategy for preventing infectious complications in patients undergoing stem cell transplantation.
The findings also support continued research into the relationship between microbial composition, pathogen colonization, and infection risk in immunocompromised populations.
Potential to Reduce Serious Infections and Sepsis
Bloodstream infections remain a major concern for patients undergoing allogeneic stem cell transplantation.
When harmful bacteria enter the bloodstream, they can trigger systemic infections that may progress to sepsis. Sepsis is a serious medical condition caused by the body’s abnormal response to infection and can result in organ dysfunction, life-threatening complications, and death.
Patients with blood cancers who undergo transplantation may face increased infection risks because of chemotherapy-related damage, immune suppression, and disruption of protective microbial populations.
Antibiotic prophylaxis and other infection-control measures remain important components of transplantation care. However, antibiotic exposure can also affect beneficial microorganisms, potentially creating conditions that favor the growth of resistant or harmful bacteria.
SER-155 is designed to complement existing infection-prevention strategies by addressing the microbiome disruption associated with these treatments.
By restoring beneficial bacterial populations and reducing the availability of resources needed by harmful pathogens, the therapy may help limit pathogen expansion and reduce the likelihood of microorganisms entering the bloodstream.
The early clinical observations involving lower pathogen levels and fewer bloodstream infections provide a rationale for further investigation.
Nevertheless, the findings should be interpreted in the context of the Phase 1 study design. Larger and appropriately controlled clinical trials will be needed to establish whether SER-155 can consistently reduce infection rates and improve clinical outcomes across broader transplant populations.
Researchers Highlight the Broader Potential of Live Biotherapeutics
The publication in Nature Medicine represents an important milestone in the development of live biotherapeutic products.
Unlike conventional medicines that generally rely on chemical compounds or biologically derived molecules, live biotherapeutics use living microorganisms as active therapeutic components.
These products are being investigated for their ability to influence biological processes within the human body, including microbial balance, immune regulation, and resistance to pathogenic organisms.
SER-155 demonstrates how specific bacterial strains can be selected and combined based on their individual biological functions to create a targeted therapeutic product.
Dr. van den Brink emphasized that the research represents an early step toward understanding the broader therapeutic potential of the microbiome.
“We are only beginning to understand the therapeutic potential of the microbiome,” he said.
The study’s findings may help support the development of additional microbiome-based treatments for patients undergoing intensive cancer therapies and other medical interventions that significantly disrupt normal microbial communities.
City of Hope’s microbiome research program is continuing to investigate new therapeutic strategies that target microbial communities, including approaches intended to improve responses to cancer immunotherapy and reduce treatment-related complications.
Recommendations for Supporting the Microbiome During Cancer Treatment
Although SER-155 remains investigational and requires additional clinical evaluation before it can become an approved treatment option, researchers have identified several general strategies that may help support microbiome health during cancer treatment.
Dr. van den Brink highlighted the importance of responsible antibiotic use, dietary fiber intake, and caution regarding over-the-counter probiotic supplements.
Antibiotic stewardship
Patients should discuss antibiotic use with their healthcare providers and follow appropriate medical guidance regarding the selection and duration of treatment.
Broad-spectrum antibiotics can affect a wide range of bacterial populations, including beneficial microorganisms that contribute to microbiome balance. Their unnecessary use may also contribute to antibiotic resistance.
Responsible antibiotic stewardship is therefore important, particularly for patients receiving cancer treatments that already place significant stress on the immune system and gastrointestinal environment.
Patients should never discontinue prescribed antibiotics or avoid necessary infection treatment without consulting their medical team.
Maintaining a fiber-rich diet
Dietary fiber is an important source of nutrients for beneficial gut bacteria.
Whole grains, fruits, vegetables, legumes, and other fiber-rich foods can support microbial diversity and promote the production of beneficial microbial metabolites.
Dr. van den Brink emphasized the importance of dietary fiber, stating, “Diet is a drug.”
He also noted that fiber-rich diets have demonstrated benefits across multiple research settings.
However, dietary recommendations for patients undergoing stem cell transplantation must be individualized. Some patients may require specific food-safety restrictions or dietary modifications during periods of severe immunosuppression.
Patients should consult their oncology and nutrition teams before making significant dietary changes.
Avoiding unsupervised probiotic supplements
Dr. van den Brink also advised caution regarding commercially available probiotic capsules, particularly for immunocompromised patients.
Over-the-counter probiotics may contain mixtures of bacterial strains that have not been specifically selected or evaluated for use in patients with severely weakened immune systems.
In certain circumstances, introducing live microorganisms through supplements could create additional infection-related risks. He also noted that some bacterial strains have been associated with less favorable outcomes in certain cancer research settings.
Consequently, patients undergoing cancer treatment or stem cell transplantation should consult their healthcare providers before taking probiotic products.
Future Research and Development at City of Hope
The SER-155 findings are part of a broader effort by City of Hope and its collaborators to translate microbiome research into new therapeutic strategies.
The institution’s research program is investigating how microbial communities influence cancer treatment responses, immune system activity, and complications associated with intensive therapies.
Future research includes additional studies and clinical trials evaluating microbiome-targeted approaches, including potential applications in improving responses to immunotherapy.
The development of defined live biotherapeutic products may offer opportunities to address specific biological problems associated with microbiome disruption rather than relying on less controlled methods of microbial restoration.
The SER-155 study provides early evidence that a scientifically designed consortium of beneficial bacteria can be administered to highly vulnerable patients, successfully establish itself within the microbiome, and potentially contribute to reducing infection-related complications.
The research was sponsored by Seres Therapeutics. The publication also disclosed that Dr. Marcel van den Brink is an inventor, receives royalties, and serves as a consultant to and shareholder of Seres Therapeutics. Additional professional relationships are disclosed in the published manuscript.
Advancing Microbiome-Based Medicine for Vulnerable Cancer Patients
The publication of the Phase 1b SER-155 clinical findings in Nature Medicine represents a significant step forward in microbiome-based therapeutic research.
The study demonstrated that a defined combination of 16 beneficial bacterial strains could be administered to patients undergoing allogeneic stem cell transplantation with an encouraging safety profile. Researchers also observed successful bacterial establishment, lower levels of harmful pathogens, and fewer bloodstream infections among treated patients.
These findings are particularly important for patients with leukemia and other blood cancers, who face substantial infectious risks during transplantation and immune recovery.
Although additional clinical studies are required to establish the efficacy and safety of SER-155 and determine its potential regulatory pathway, the results support further investigation of targeted live biotherapeutics as an approach to infection prevention.
Through its collaboration with Memorial Sloan Kettering Cancer Center and Seres Therapeutics, City of Hope is contributing to the development of a new therapeutic strategy that moves beyond conventional infection prevention toward addressing the underlying microbiome disruption.
As research advances, scientifically engineered bacterial therapies could potentially become an important addition to supportive cancer care, helping protect vulnerable patients against serious infections while supporting microbiome health and recovery.
About City of Hope
City of Hope’s mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies.
With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked among the nation’s top cancer centers by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work.
City of Hope’s growing national system includes its Los Angeles campus, Orange County, California, campus, a network of clinical care locations across Southern California and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM.