(Press-News.org) LOS ANGELES — A team of researchers from City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the U.S., and The University of Texas M.D. Anderson Cancer Center, have reported safety and efficacy results from a Phase 1 trial that featured a personalized vaccine to treat lymphoplasmacytic lymphoma, a rare and slow-growing type of blood cancer, according to a study published recently in Nature Communications.
The current approach to lymphoplasmacytic lymphoma care is active surveillance of a patient’s possible symptoms. There is a median time of 3.5 years from diagnosis to progression of symptoms — such as fever, night sweats, weight loss and fatigue — that require chemotherapy.
“By doing an early intervention with the vaccine, we nearly doubled the disease-free progression time to an average of just under seven years,” said Larry Kwak, M.D., Ph.D., director of City of Hope’s Toni Stephenson Lymphoma Center within the Hematologic Malignancies Research Institute, who developed the vaccine and is the study’s corresponding author. “In addition to being effective, the vaccine appears to be safe. It didn’t have any of the harsh side effects associated with other types of common cancer treatments.”
Toxicity among trial participants was also limited, Dr. Kwak said. That’s because the vaccine uses patient-specific biologic components called tumor neoantigens that can help the body mount an immune response to a particular tumor type.
The clinical trial, led by M.D. Anderson, enrolled nine patients, who were able to tolerate the therapy without negative side effects. After a median follow up of 7.5 years, all of the patients had stable disease and more than half had not progressed to a symptomatic state.
“Using sophisticated technology called single-cell sequencing, we could see that these personalized vaccines activated T cells in the tumor microenvironment, which help destroy tumor cells,” said Dr. Kwak, who is also the deputy director of City of Hope's comprehensive cancer center and the Dr. Michael Friedman Professor in Translational Medicine. “Furthermore, we saw that the tumor cells rely on signaling from myeloid cells to survive, which we didn’t know before, and the vaccine reduced that protumoral signaling, too.”
According to Dr. Kwak, disease progression was halted and one patient had a minor reduction in tumor shrinkage. The research teams believe this is because two different subtypes of cells give rise to tumors in lymphoplasmacytic lymphoma — mature B cells and plasma cells — and the vaccine only had an effect on the B cell population.
“The takeaway from that observation is that when we do the next phase clinical trial, we will want to combine the vaccine with another agent that does have more of a direct effect on plasma cells, like a monoclonal antibody,” he said.
Dr. Kwak and the research team are working on the next generation of the vaccine for a possible clinical trial that may take place at City of Hope. As part of a Sponsored Research Agreement with Renhaim Inc., Dr. Kwak and team plan to adapt the vaccine to an mRNA platform, which has become a new frontier for vaccine production since the original was developed using DNA nearly a decade ago. The team is also exploring additional therapies to pair with the neoantigen for more vaccine efficacy. Dr. Kwak is a paid consultant with Renhaim Inc.
The neoantigen vaccine research builds upon three decades of investigations by Dr. Kwak, who is a world-renowned physician and pioneering scientist in immunology and cancer vaccines. Dr. Kwak was named one of TIME magazine’s “100 Most Influential People” in 2010 for his work in cancer immunology.
In 2011, Dr. Kwak and colleagues published research in the Journal of Clinical Oncology on the first iteration of the neoantigen vaccine. It was a protein-based vaccine for follicular lymphoma that garnered positive results.
“It was actually one of the first positive cancer vaccine positive trials in the field, but 15 years ago, no drug company was interested in talking with us about a personalized vaccine,” Dr. Kwak said. He noted that the “one drug for one patient” model was a tough sell until CAR T cell therapies set a precedent for individualized cancer medicines. “Now they're much more open to it. I think the future of cancer vaccines is really in this kind of setting, where we’ve shown the effectiveness of early intervention as a way to prolong and maybe even prevent progression to symptomatic disease.”
The research reported in the Nature Communications paper, “Personalized neoantigen vaccines as early intervention in untreated patients with lymphoplasmacytic lymphoma: a non-randomized phase 1 trial,” was supported by the National Cancer Institute and the International Waldenstrom’s Macroglobulinemia Foundation.
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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 U.S. 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 top 5 in the nation for cancer care by U.S. News & World Report at its core, City of Hope brings a uniquely integrated model to patients, spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, 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. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.
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