(Press-News.org) TAMPA, Fla. – Prostate cancer frequently metastasizes to the bone and is incurable. Moffitt Cancer Center researchers are working to identify new treatment options for this subset of patients. In a new article published today in Science Advances, a team of Moffitt scientists demonstrates that chimeric antigen receptor T-cell (CAR T) therapy is an effective antitumor approach in mouse models of bone metastatic prostate cancer.
“Bone metastatic prostate cancer is an incurable disease that significantly impacts patient lives through extreme bone pain,” said study co-lead author Conor Lynch, Ph.D., interim chair of the Tumor Biology Department at Moffitt. “Bisphosphonates such as zoledronate help mitigate this problem and reduce pathological fracture but have little impact on patient survival. Therefore, new treatment options are urgently needed.”
Moffitt researchers wanted to investigate the possibility of using CAR T-cell therapy for bone metastatic prostate cancer and whether this treatment approach could be enhanced by combining it with zoledronate. CAR T therapy is relatively new in cancer treatment. This form of cellular immunotherapy was first approved in 2017 for certain blood cancers. For this therapy, T cells isolated from patients are genetically engineered to target a tumor-specific marker. The T cells are expanded in culture and infused back into the patient where they can target tumor cells for destruction.
In this collaborative study between the labs of Lynch and Daniel Abate-Daga, Ph.D., co-first authors Jeremy Frieling, Ph.D., and Leticia Tordesillas, Ph.D., used a specific subtype of T cell called gamma/delta T cells.
“These are relatively less studied than the conventional alpha/beta T cells but have attracted substantial interest from the biotech sector in recent years,” said co-lead author Abate-Daga, associate member of the Department of Immunology and scientific director of the Cell Therapies Core Facility at Moffitt.
The researchers created CAR T cells that were specific to the tumor biomarker called prostate stem cell antigen (PSCA) that is highly expressed in bone metastatic prostate cancer. They demonstrated that the CAR T cells killed prostate cancer cells in cell culture and stimulated the production of chemical messengers that stimulate immune cell activity.
They next moved their experiment to mouse models and showed that the CAR T cells significantly decreased the size of tumors and improved survival with limited toxicity. Additionally, pretreatment of the mice with zoledronate helped activate the CAR T cells through a CAR-independent mechanism, allowing for increased ability to recognize and destroy tumors. Importantly, in addition to eliminating tumors, this treatment was able to preserve the health of the bones.
“To our knowledge, this study is the first to evaluate gamma/delta T cells for expressing chimeric antigen receptor and treating bone metastatic prostate cancer. This strategy offers a dual-targeting mechanism to eradicate bone metastatic prostate cancer, a strategy that can be quickly translated to the clinical setting,” Abate-Daga said.
The study was supported by the National Cancer Institute (P30CA07629, R01CA241169 and U01CA244101), Department of Defense Prostate Cancer Research Program (W81XWH-18-2-0013, W81XWH-18-2-0015, W81XWH-18-2-0016, W81XWH-18-2-0017, W81XWH-18-2-0018 and W81XWH-18-2-0019) and a team science award from Moffitt Cancer Center.
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 53 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 7,800 team members, Moffitt has an economic impact in the state of $2.4 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter, Instagram and YouTube.
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Alexandria, VA, USA – The International Association for Dental Research (IADR) and American Association for Dental, Oral, and Craniofacial Research (AADOCR) have announced the publication in July 2023 of a Special Issue of Journal of Dental Research (JDR) entitled, “Aging and Oral Health.” It will feature Bei Wu, New York University, USA and Ana Paula Vieira Colombo, Federal University of Rio de Janeiro, Brazil as Guest Editors.
Several articles that will be included in the issue are currently available for viewing Online First at the JDR website, including:
Diabetes, Edentulism, and Cognitive Decline: ...
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“A rapid and accurate onsite approach for determining FFR-CT should address challenges encountered in the clinical ...
MINNEAPOLIS – How are you sleeping? A new study has found the transition from daylight saving time to standard time, when one hour is gained overnight, was associated with a brief increase in sleep disorders such as difficulty going to sleep or staying asleep, but there was no such association when an hour is lost in the change from standard time to daylight saving time. The study is published in the May 3, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. It also found a small difference in the amount of sleep people get depending ...
When Doc Brown fed his DeLorean food scraps in Back to the Future as fuel, it seemed like crazy science fiction.
Now science is taking over that fiction as UBC Okanagan researchers are looking at the potential of using fruit waste—both solid and leachate—to power fuel cells.
While the energy extracted from food scraps still pales in comparison to solar or wind power, researchers are working towards purifying and improving the energy output of discarded food, particularly fruit waste—an item that is in abundance in the agricultural belt of the Okanagan Valley.
According ...
MINNEAPOLIS/ST. PAUL (05/03/2023) — Published in the peer-reviewed journal Alcohol: Clinical & Experimental Research, University of Minnesota Medical School researchers found people with an anxiety or major depression disorder experience greater alcohol use disorder symptoms and problems in comparison to people without those disorders — even at the same levels of drinking. This finding might help to explain why those who develop an anxiety or mood disorder are at heightened risk ...
Researchers at West Virginia University have uncovered critical data showing bariatric surgery as a treatment method for patients with nonalcoholic fatty liver disease has a significant impact on improving clinical outcomes. The study, led by Dr. Shailendra Singh, included thousands of patients diagnosed with NAFLD, a condition that is seeing an upsurge and contributes to multiple other afflictions.
While bariatric surgery has long been associated with reducing cardiovascular disease and death in patients with obesity, the research team set out to explore whether the ...
Two-photon microscopy (TPM) has revolutionized the field of biology by enabling researchers to observe complex biological processes in living tissues at high resolution. In contrast to traditional fluorescence microscopy techniques, TPM makes use of low-energy photons to excite fluorescent molecules for observation. This, in turn, makes it possible to penetrate the tissue much more deeply, and ensures that the fluorescent molecules, or fluorophores, are not permanently damaged by the excitation laser.
However, some biological processes are simply too fast to be recorded, even with state-of-the-art TPMs. One of the design parameters that limits the performance of a TPM is ...
The latest issues of three of the American Psychiatric Association’s journals, The American Journal of Psychiatry, Psychiatric Services and Focus are now available online.
The May issue of The American Journal of Psychiatry focuses on treatments, with articles presenting issues related to psychedelics, trichotillomania, social anxiety disorder, schizophrenia, and opioid use disorder. Highlights include:
Psychedelics as Transformative Therapeutics.
Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder.
Attention Bias Modification Treatment Versus a Selective ...
Long-term exposure to fine particulate matter air pollution was associated with an increase in hospital procedures in heart failure patients, according to a study published May 3, 2023, in the open-access journal PLOS ONE by Samantha Catalano from the University of North Carolina at Chapel Hill, USA, and colleagues.
Tiny airborne particles smaller than 2.5μm in diameter (PM2.5) are air pollutants generated by traffic, industry activity, combustion, and more. Though exposure to PM2.5 has been associated with illness and death worldwide, ...
The first modern humans spread across Europe in three waves during the Paleolithic, according to a study published May 3, 2023 in the open-access journal PLOS ONE by Ludovic Slimak of the CNRS and University of Toulouse III, France.
The archaeological record of Paleolithic Europe leaves many open questions regarding the nature of the arrival of modern humans into the region and the nature of how these newcomers interacted with the resident Neanderthal populations. In this study, Slimak compared records of stone tool technology across western Eurasia to document the sequence of early human activity in the region.
This study primarily focused on ...
