Link Between Melanoma and Estrogen Could Lead to New Therapeutic Approach
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Sarah Avery
Director, Duke Health News Office
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Mustafa Khasraw to Lead U.S. Arm of International Glioblastoma Trial
Mustafa Khasraw, MD, deputy director of the Duke Cancer Institute Center for Cancer Immunotherapy, is at the forefront of a promising clinical trial aimed at improving outcomes for patients with glioblastoma.Glioblastoma is a highly aggressive form of brain cancer known for its poor prognosis, with most patients surviving only 12 to 18 months after diagnosis. Approximately 75 percent of patients die within a year, and more than 95 percent die within three years. Traditional treatments have had limited success, necessitating innovative approaches to extend survival and improve quality of life.Based on existing research, a novel immunotherapy regimen combining nivolumab and relatlimab – previously used to treat melanoma – has been identified as a potential neoadjuvant treatment for glioblastoma. The Glioblastoma Immunotherapy Advancement with Nivolumab and Relatlimab Trial (GIANT) will be conducted at Duke in the United States and at the Peter MacCallum Cancer Center in Melbourne, Australia.Khasraw is the study chair and principal investigator for the U.S. portion of the GIANT trial, with Jim Whittle BSc., MBBS (Hons), FRACP, as the Australian co-principal investigator."Research from our group and others has shown that immunotherapy given before the surgical removal of cancer can reprogram the immune response, even in recurrent gliomas,” Khasraw said. “With this trial, we are moving that approach earlier, into newly diagnosed disease, to test whether this combination of immune checkpoint blockades can drive stronger and more lasting improvements in patient outcomes."The GIANT trial will start enrollment this summer, beginning with a small cohort of six to 12 patients with newly diagnosed isocitrate dehydrogenase (IDH) wild-type glioblastoma or those who have not received prior radiation or chemotherapy. These patients will receive the neoadjuvant immunotherapy regimen. If deemed safe, the trial will expand to include up to 80 participants, who will be randomly assigned to receive one of two treatment protocols.Khasraw's team at Duke will lead the analysis of tumor samples before and after treatment using advanced spatial technologies. A research consortium across the U.S. – including Duke, University of California Los Angeles, University of California San Francisco, Memorial Sloan Kettering Cancer Center, and MD Anderson Cancer Center – and Australian academic institutions led by the Peter McCallum Cancer Center has built a network for comprehensive biomarker and correlative science analysis, which will provide useful biological insights into the treatment's impact.“This trial will be significant in helping us better understand cancer biology,” Khasraw said. “We stand to gain valuable insights from this research that could help shape future research and therapies for glioblastoma.”
New Understanding of Antibody Activity Shows Promise for Improved Immunotherapies
New research indicates antibodies produced in tertiary lymphoid structures (TLS) could help target tumor cells and cells in the surrounding environment, enhancing existing immunotherapies for cancer patients.Jose Conejo-Garcia, MD, PhD, an immunologist and Duke Cancer Institute member, led this study and presented findings at the 2025 American Associate for Cancer Research Immuno-Oncology meeting.While most cancer immunotherapies focus on T cells, which play a vital role in a person’s immune system and help protect the body from diseases like cancer, Conejo-Garcia and his team focused on how B cells could factor into these treatments. B cells are a type of white blood cell that produces antibodies to help fight pathogens in the body.“We do not understand why immune checkpoint inhibitors do not work against ovarian cancer, which is an immunogenic disease,” he said. “We’ve found that patients with evident TLS activity had improved outcomes, but we wanted to understand why.”Using ovarian cancer samples, Conejo-Garcia and his team extracted DNA specifically from TLS to examine how antibodies produced in TLS worked. They found TLS produced highly clonal immunoglobulin A (IgA) and immunoglobulin (IgG) antibodies, which the team previously showed are important to maintain immune pressure against malignant progression.The team then produced one of these antibodies and used it to restrain the growth of the tumor where the antibody originated. These discoveries indicate that immunologists could trigger TLS in ovarian cancer cells to improve immunotherapy responses.“We are applying this approach to clone antibodies produced in intra-tumoral TLS that could serve as novel immunotherapeutic tools, in ovarian cancer and other tumors,” he said.Conejo-Garcia and his team continue to examine how cloning antibodies could impact treatment for cancer patients. The team was recently issued a notice of award from the U.S. Department of Defense, as well as grants for similar methods to identify ways to tailor this approach for cancer prevention.“We hope to characterize T cells and plasma cells from ovarian tumors, as well as develop therapies based on antibodies and T cell receptors,” Conejo-Garcia said. “We are collaborating with other investigators at Duke to define the potential of tumor-derived antibodies to develop novel cellular immunotherapies or antibody-drug conjugates, with a promising lead so far.”
Related News
Mustafa Khasraw to Lead U.S. Arm of International Glioblastoma Trial
Mustafa Khasraw, MD, deputy director of the Duke Cancer Institute Center for Cancer Immunotherapy, is at the forefront of a promising clinical trial aimed at improving outcomes for patients with glioblastoma.Glioblastoma is a highly aggressive form of brain cancer known for its poor prognosis, with most patients surviving only 12 to 18 months after diagnosis. Approximately 75 percent of patients die within a year, and more than 95 percent die within three years. Traditional treatments have had limited success, necessitating innovative approaches to extend survival and improve quality of life.Based on existing research, a novel immunotherapy regimen combining nivolumab and relatlimab – previously used to treat melanoma – has been identified as a potential neoadjuvant treatment for glioblastoma. The Glioblastoma Immunotherapy Advancement with Nivolumab and Relatlimab Trial (GIANT) will be conducted at Duke in the United States and at the Peter MacCallum Cancer Center in Melbourne, Australia.Khasraw is the study chair and principal investigator for the U.S. portion of the GIANT trial, with Jim Whittle BSc., MBBS (Hons), FRACP, as the Australian co-principal investigator."Research from our group and others has shown that immunotherapy given before the surgical removal of cancer can reprogram the immune response, even in recurrent gliomas,” Khasraw said. “With this trial, we are moving that approach earlier, into newly diagnosed disease, to test whether this combination of immune checkpoint blockades can drive stronger and more lasting improvements in patient outcomes."The GIANT trial will start enrollment this summer, beginning with a small cohort of six to 12 patients with newly diagnosed isocitrate dehydrogenase (IDH) wild-type glioblastoma or those who have not received prior radiation or chemotherapy. These patients will receive the neoadjuvant immunotherapy regimen. If deemed safe, the trial will expand to include up to 80 participants, who will be randomly assigned to receive one of two treatment protocols.Khasraw's team at Duke will lead the analysis of tumor samples before and after treatment using advanced spatial technologies. A research consortium across the U.S. – including Duke, University of California Los Angeles, University of California San Francisco, Memorial Sloan Kettering Cancer Center, and MD Anderson Cancer Center – and Australian academic institutions led by the Peter McCallum Cancer Center has built a network for comprehensive biomarker and correlative science analysis, which will provide useful biological insights into the treatment's impact.“This trial will be significant in helping us better understand cancer biology,” Khasraw said. “We stand to gain valuable insights from this research that could help shape future research and therapies for glioblastoma.”
New Understanding of Antibody Activity Shows Promise for Improved Immunotherapies
New research indicates antibodies produced in tertiary lymphoid structures (TLS) could help target tumor cells and cells in the surrounding environment, enhancing existing immunotherapies for cancer patients.Jose Conejo-Garcia, MD, PhD, an immunologist and Duke Cancer Institute member, led this study and presented findings at the 2025 American Associate for Cancer Research Immuno-Oncology meeting.While most cancer immunotherapies focus on T cells, which play a vital role in a person’s immune system and help protect the body from diseases like cancer, Conejo-Garcia and his team focused on how B cells could factor into these treatments. B cells are a type of white blood cell that produces antibodies to help fight pathogens in the body.“We do not understand why immune checkpoint inhibitors do not work against ovarian cancer, which is an immunogenic disease,” he said. “We’ve found that patients with evident TLS activity had improved outcomes, but we wanted to understand why.”Using ovarian cancer samples, Conejo-Garcia and his team extracted DNA specifically from TLS to examine how antibodies produced in TLS worked. They found TLS produced highly clonal immunoglobulin A (IgA) and immunoglobulin (IgG) antibodies, which the team previously showed are important to maintain immune pressure against malignant progression.The team then produced one of these antibodies and used it to restrain the growth of the tumor where the antibody originated. These discoveries indicate that immunologists could trigger TLS in ovarian cancer cells to improve immunotherapy responses.“We are applying this approach to clone antibodies produced in intra-tumoral TLS that could serve as novel immunotherapeutic tools, in ovarian cancer and other tumors,” he said.Conejo-Garcia and his team continue to examine how cloning antibodies could impact treatment for cancer patients. The team was recently issued a notice of award from the U.S. Department of Defense, as well as grants for similar methods to identify ways to tailor this approach for cancer prevention.“We hope to characterize T cells and plasma cells from ovarian tumors, as well as develop therapies based on antibodies and T cell receptors,” Conejo-Garcia said. “We are collaborating with other investigators at Duke to define the potential of tumor-derived antibodies to develop novel cellular immunotherapies or antibody-drug conjugates, with a promising lead so far.”