The article describes a groundbreaking study that has shown promising results in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, including commercially available CAR T cell therapies. The new enhanced CAR T cell therapy, dubbed huCART19-IL18, was found to be highly effective in 81% of patients and resulted in complete remission in 52%. This is a significant improvement over traditional CAR T cell therapies, which have been shown to result in long-term remission in only around 50% of patients.

The study, led by researchers at the University of Pennsylvania, used a new process that shortens the manufacturing time for the CAR T cells to just three days. This means that patients with aggressive, fast-growing cancers can begin CAR T cell therapy quicker than is currently possible with standard manufacturing times of nine to 14 days.

The addition of interleukin 18 (IL18) to the CAR T cells enhanced their ability to attack cancer cells and protected them from immune suppression and T cell exhaustion. The researchers also found that the type of CAR T cell therapy patients previously received may impact the efficacy of huCART19-IL18.

This study represents a significant development in the ongoing evolution of CAR T cell therapy, as it is the first time a cytokine-enhanced CAR T has been tested in patients with blood cancer. The researchers believe that incorporating cytokine secretion into CAR T cell design will have broad implications for enhancing cellular therapies, even beyond blood cancers.

The study has already led to several other clinical trials being planned, including studies for acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Another trial for non-Hodgkin’s lymphoma using a similar IL18-armored CAR T cell product is currently enrolling patients. On the manufacturing side, the team is partnering with a Penn spinout company to improve the process for how these CAR T cells are created and expanded in the laboratory before being reinfused into the patient.

Overall, this study has shown promise in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, and further research is needed to fully understand its potential.

Early Cancer Detection: New Algorithms Revolutionize Primary Care

Two groundbreaking predictive algorithms have been developed to help General Practitioners (GPs) identify patients who may have undiagnosed cancer, including hard-to-detect liver and oral cancers. These advanced models use information about a patient’s health conditions and simple blood tests to accurately predict their chances of having an undiagnosed cancer.

The National Health Service (NHS) currently uses algorithms like the QCancer scores to combine relevant patient data and identify individuals at high risk of having undiagnosed cancer, allowing GPs and specialists to call them in for further testing. Researchers from Queen Mary University of London and the University of Oxford have created two new algorithms using anonymized electronic health records from over 7.4 million adults in England.

The new models are significantly more sensitive than existing ones, potentially leading to better clinical decision-making and earlier cancer diagnosis. Crucially, these algorithms incorporate the results of seven routine blood tests as biomarkers to improve early cancer detection. This approach makes it easier for patients to receive treatment at much earlier stages, increasing their chances of survival.

Compared to the QCancer algorithms, the new models identified four additional medical conditions associated with an increased risk of 15 different cancers, including liver, kidney, and pancreatic cancers. The researchers also found two additional associations between family history and lung cancer and blood cancer, as well as seven new symptoms of concern (itching, bruising, back pain, hoarseness, flatulence, abdominal mass, dark urine) associated with multiple cancer types.

The study’s lead author, Professor Julia Hippisley-Cox, said: “These algorithms are designed to be embedded into clinical systems and used during routine GP consultations. They offer a substantial improvement over current models, with higher accuracy in identifying cancers – especially at early, more treatable stages.”

Dr Carol Coupland, senior researcher and co-author, added: “These new algorithms for assessing individuals’ risks of having currently undiagnosed cancer show improved capability of identifying people most at risk of having one of 15 types of cancer based on their symptoms, blood test results, lifestyle factors, and other information recorded in their medical records.”

In a groundbreaking study published in the Proceedings of the National Academy of Sciences (PNAS), University of Oklahoma researchers have made a significant discovery about what makes glioblastoma, the deadliest form of brain cancer, so aggressive. The findings center on ZIP4, a protein that transports zinc throughout the body and sets off a chain reaction that drives tumor growth.

Glioblastomas account for about half of all malignant brain tumors, with a median survival rate of 14 months. Surgery is often challenging, and patients almost always experience a relapse. By better understanding why these brain tumors are so aggressive, researchers hope to open up paths for new treatments.

In normal conditions, ZIP4 plays a positive role, transporting and maintaining the right amount of zinc for good health. However, when brain cancer is present, ZIP4 takes on a different role. In the case of glioblastoma, it triggers a series of events that contribute to the tumor’s aggressive growth.

“Everything starts with the fact that ZIP4 is overexpressed in glioblastoma,” says senior author Min Li, Ph.D., a professor of medicine, surgery, and cell biology at the University of Oklahoma College of Medicine. “That triggers all these downstream events that help the tumor to grow.”

Li’s research team tested a small-molecule inhibitor that targets ZIP4 and TREM1, a protein involved in immune responses. The inhibitor attached to both proteins, stopping their actions and slowing tumor growth. This suggests that ZIP4 and TREM1 may be promising therapeutic targets.

Neurosurgeon Ian Dunn, M.D., executive dean of the OU College of Medicine and co-author of the study, says the findings are an encouraging step toward combating this debilitating cancer. “These results are really exciting in such a debilitating cancer. The hope and promise is to translate these findings to novel treatment approaches to improve the lives of our patients.”

This discovery is significant not only for glioblastoma but also for pancreatic cancer research, as ZIP4 has been a focus of Li’s work on this disease for many years. He found that overexpression of ZIP4 causes pancreatic cancer cells to be more resistant to chemotherapy and prompts tumor cells to transform themselves so they can stealthily travel to the body’s other organs.

The researchers hope that their findings will lead to new treatment approaches for glioblastoma and potentially other types of cancer, improving the lives of patients affected by these devastating diseases.