News | New antibody therapy shows activity in ovarian cancer, revealing how the immune counterattack begins
A King's College London team has shown how a new antibody therapy reactivates patients' immune systems against ovarian cancer. Led by Professor Sophia Karagiannis, the study provides key evidence on patients' immune-response mechanisms and supports further clinical development.
Almost all cancer antibody therapies currently used in clinical practice are based on IgG, but IgG has not shown sustained effectiveness in ovarian cancer. King's researchers pioneered an IgE-based antibody. IgE normally participates in allergic responses and immunity to parasitic infections and binds very tightly to immune cells in tissues. The team sought to use this property to produce strong immune activation in solid tumors.
The study focused on an antibody called MOv18 IgE and evaluated how it acts in the immune systems of ovarian cancer patients. MOv18 IgE reversed tumor-mediated immune suppression and reactivated impaired anticancer responses by stimulating different immune-cell populations.
A central part of the study was an in-depth analysis of macrophages. These cells normally remove pathogens but can be corrupted within the tumor environment and may support tumor growth. The team first exposed macrophages from healthy donors to malignant fluid from the abdominal cavities of ovarian cancer patients, then isolated native macrophages from patient samples. Regardless of their origin, macrophages became immunosuppressed in the tumor environment. MOv18 IgE, however, bound to and activated them, restoring their ability to kill ovarian cancer cells.
MOv18 IgE activation also affected another key immune population, T cells. Tumor-reprogrammed macrophages usually suppress T-cell activity. MOv18 IgE removed this suppression, allowing T cells to resume long-term immune surveillance of tumors.
First author Dr. Gabriel Osborn said the tumor environment caused macrophages and T cells to form an "immunosuppressive network." MOv18 IgE disrupted this network and reactivated both cell types against cancer. "This is the first patient-level evidence that IgE-mediated macrophage stimulation can activate the broader immune system."
Further clinical evidence came from tumor biopsies from two patients in the MOv18 IgE Phase Ia trial. Post-treatment samples contained substantially more macrophages and T cells, suggesting that both are central to the antibody's antitumor response. The trial was conducted by the NIHR Guy's and St Thomas' Clinical Research Facility with the Cancer Research UK (CRUK) Centre for Drug Development. At a low dose, MOv18 IgE reduced the tumor of one patient who had not responded to standard treatment.
"Understanding a treatment's biology is essential to bringing it to patients," Professor Karagiannis said. "We found that immune cells suppressed in the tumor microenvironment can be directed by IgE to recognize and attack cancer cells again." She added that the team is studying more IgE antibodies in different cancers and patient groups.
Study collaborator Dr. Debra Josephs, consultant oncologist at Guy's and St Thomas' NHS Foundation Trust, added: "Our early MOv18 IgE research showed that macrophage activation and migration into tumor tissue are essential to its effect. This study further clarifies the mechanism and provides important support for clinical development of this new antibody."
MOv18 IgE research also received support from Cancer Research UK, the UK Medical Research Council (MRC), Breast Cancer Now, the City of London Cancer Research Centre and the King’s Health Partners Centre for Translational Medicine.
News | New antibody therapy shows activity in ovarian cancer, revealing how the immune counterattack begins
News | New antibody therapy shows activity in ovarian cancer, revealing how the immune counterattack begins
A King's College London team has shown how a new antibody therapy reactivates patients' immune systems against ovarian cancer. Led by Professor Sophia Karagiannis, the study provides key evidence on patients' immune-response mechanisms and supports further clinical development.
Almost all cancer antibody therapies currently used in clinical practice are based on IgG, but IgG has not shown sustained effectiveness in ovarian cancer. King's researchers pioneered an IgE-based antibody. IgE normally participates in allergic responses and immunity to parasitic infections and binds very tightly to immune cells in tissues. The team sought to use this property to produce strong immune activation in solid tumors.
The study focused on an antibody called MOv18 IgE and evaluated how it acts in the immune systems of ovarian cancer patients. MOv18 IgE reversed tumor-mediated immune suppression and reactivated impaired anticancer responses by stimulating different immune-cell populations.
A central part of the study was an in-depth analysis of macrophages. These cells normally remove pathogens but can be corrupted within the tumor environment and may support tumor growth. The team first exposed macrophages from healthy donors to malignant fluid from the abdominal cavities of ovarian cancer patients, then isolated native macrophages from patient samples. Regardless of their origin, macrophages became immunosuppressed in the tumor environment. MOv18 IgE, however, bound to and activated them, restoring their ability to kill ovarian cancer cells.
MOv18 IgE activation also affected another key immune population, T cells. Tumor-reprogrammed macrophages usually suppress T-cell activity. MOv18 IgE removed this suppression, allowing T cells to resume long-term immune surveillance of tumors.
First author Dr. Gabriel Osborn said the tumor environment caused macrophages and T cells to form an "immunosuppressive network." MOv18 IgE disrupted this network and reactivated both cell types against cancer. "This is the first patient-level evidence that IgE-mediated macrophage stimulation can activate the broader immune system."
Further clinical evidence came from tumor biopsies from two patients in the MOv18 IgE Phase Ia trial. Post-treatment samples contained substantially more macrophages and T cells, suggesting that both are central to the antibody's antitumor response. The trial was conducted by the NIHR Guy's and St Thomas' Clinical Research Facility with the Cancer Research UK (CRUK) Centre for Drug Development. At a low dose, MOv18 IgE reduced the tumor of one patient who had not responded to standard treatment.
"Understanding a treatment's biology is essential to bringing it to patients," Professor Karagiannis said. "We found that immune cells suppressed in the tumor microenvironment can be directed by IgE to recognize and attack cancer cells again." She added that the team is studying more IgE antibodies in different cancers and patient groups.
Study collaborator Dr. Debra Josephs, consultant oncologist at Guy's and St Thomas' NHS Foundation Trust, added: "Our early MOv18 IgE research showed that macrophage activation and migration into tumor tissue are essential to its effect. This study further clarifies the mechanism and provides important support for clinical development of this new antibody."
MOv18 IgE research also received support from Cancer Research UK, the UK Medical Research Council (MRC), Breast Cancer Now, the City of London Cancer Research Centre and the King’s Health Partners Centre for Translational Medicine.
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