A teenage girl's incurable cancer has been cleared from her body in the first use of a revolutionary new type of medicine.
All other treatments for Alyssa's leukaemia had failed.
So doctors at Great Ormond Street Hospital used "base editing" to perform a feat of biological engineering to build her a new living drug.
Six months later the cancer is undetectable, but Alyssa is still being monitored in case it comes back.
A new therapy that makes the immune system kill bone marrow cancer cells was successful in as many as 73% of patients in two clinical trials, according to researchers from The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.
The therapy, known as a bispecific antibody, binds to both T cells and multiple myeloma cells and directs the T cells—white blood cells that can be enlisted to fight off diseases—to kill multiple myeloma cells. The researchers described this strategy as "bringing your army right to the enemy."
The success of the off-the-shelf immunotherapy, called talquetamab, was even seen in patients whose cancer was resistant to all approved multiple myeloma therapies. It uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells known as GPRC5D.
Talquetamab was tested in phase 1 and phase 2 trials. The phase 1 trial, which was reported in the New England Journal of Medicine, established two recommended doses that were tested in the Phase 2 trial. The results of the Phase 2 trial were reported at the American Society of Hematology annual meeting on Saturday, December 10. The study participants had all been previously treated with at least three different therapies without achieving lasting remission, suggesting talquetamab could offer new hope for patients with hard-to-treat multiple myeloma.
Researchers from the University at Buffalo School of Pharmacy and Pharmaceutical Sciences recently published in Molecular & Cellular Proteomics, describing their work in identifying key metabolic regulators involved in cancer cell resistance to gemcitabine (Gem), a standard-of-care chemotherapy for pancreatic dual adenocarcinoma (PDAC), the most lethal type of pancreatic cancer.
Robert M. Straubinger, Ph.D., UB Distinguished Professor, and Jun Qu, Ph.D., Professor, both of the Department of Pharmaceutical Sciences, led the research, which included William J. Jusko, Ph.D., SUNY Distinguished Professor, and several of his lab members.
Gemcitabine resistance (GemR) can develop clinically during chemotherapy, resulting in poor patient prognosis. Understanding the molecular mechanisms of Gem resistance has been challenging.
Straubinger and Qu collaborated on the application of a cutting-edge comprehensive, quantitative proteomic analysis approach to identify key metabolic regulators of Gem resistance in PDAC. Their team systematically examined PDAC cancer cells and identified several therapeutic vulnerabilities of drug resistance that could be targeted to improve therapeutic outcomes for PDAC patients experiencing Gem resistance.
Pancreatic adenocarcinoma does not respond well to current treatments or to newer immunotherapies that have worked well in some cancers. Gem is the mainstay drug for PDAC patients but provides only modest survival benefits. Clinically, development of Gem resistance can be rapid and compromises its efficacy.
Coming off the success of its mRNA vaccine for COVID-19, Moderna announced on Dec. 13 that it achieved encouraging results when it turned its vaccine technology against cancer.
The company reported in a release that among 157 people with stage 3 or stage 4 melanoma, a personalized cancer vaccine that Moderna developed with Merck—created using mRNA genetic material from each patient’s respective tumors—reduced the risk of recurrence or death by 44% compared to standard care.
“For the first time ever, we have evidence that it’s possible to develop a functional immune response that can treat patients’ cancer from a randomized controlled trial,” says Dr. Stephen Hoge, president of Moderna.
Read more here: https://www.nature.com/articles/d41586-022-04465-y(Nature) Elaborately engineered immune cells can not only recognize cancer cells, but also evade defences that tumours use to fend off attacks, researchers have found.
Two studies published today in Science1,2 build on the success of chimeric antigen receptor (CAR)-T cancer therapies, which use genetically altered T cells to seek out tumours and mark them for destruction. These treatments have the potential to lead to long-lasting remission, but are not successful for everyone, and have so far been effective against only a small number of cancers.
Glioblastomas (GBMs) are incurable brain tumors with a prognosis of about one-and-a half years on average. They are highly resistant to treatment and have defied all attempts at precision therapy.
In their study publishing December 20 in Nature Cancer, first author Lin Wang, Ph.D. and senior author Aaron Diaz, Ph.D., found that phenotype switching, as opposed to genetic evolution, may be the escape mechanism that explains the failure of precision therapies to date. They found that some cells shift to a mesenchymal, radiation-resistant phenotype (state) as a stress response following standard therapy.
"We asked if there is another mechanism that explains therapeutic resistance," said Diaz, associate professor of neurological surgery at the UCSF Weill Institute for Neurosciences. "Our study concludes that, rather than a genetic evolution, there is a phenotypic plasticity or transition which allows these cells to evade therapy."
To identify what drives treatment resistance to standard therapy, as well as the cellular source of recurrent disease, UCSF researchers used single-nucleus RNA, open-chromatin, spatial profiling to analyze 86 primary-recurrent, patient-matched, paired GBM specimens. This unprecedented cohort represented decades of biobanking at UCSF.
With access to thirty years' worth of GBM's, the scientists were able to present novel cell-intrinsic and cell-extrinsic targets as well as a single-cell multi-omics atlas of GBM under therapy. This was the first time that researchers were able to comprehensively map intra-cellular signaling in the tumor-anatomical niches of recurrent GBM and identify novel cell-extrinsic therapeutic targets.
The 86 specimens contained the cellular tumor and adjacent non-malignant tissue from the surgical margin. This unique cohort enabled Diaz and his team to analyze communications between malignant and non-malignant glia. They found that cells in this surgical margin acted as niches of recurrence where non-malignant glia were broadcasting pro-growth signals that influenced the tumor cells to regrow. These paracrine (cell extrinsic) signals stimulated the activator protein (AP1) pathway, leading to mesenchymal transition, therapy resistance and tumor recurrence.
Researchers at Indiana University School of Medicine are learning more about ways to prevent serious side effects from chemotherapy used to treat breast cancer patients. The work done by the Schneider lab at the Vera Bradley Foundation Center for Breast Cancer Research at the IU Melvin and Bren Simon Comprehensive Cancer Center and led by Xi Wu, Ph.D. was recently published in Nature Communications.
Anthracyclines belong to a class of chemotherapy agents used to treat a variety of cancers and remain an important part of therapy for patients with high-risk breast cancer. While effective in improving cure rates, they can also cause serious heart damage, including heart failure, which is often irreversible.
"This is of crucial clinical importance for breast cancer patients as there are no proven strategies for prevention or interventions for cardiotoxicity," said Wu, a former Vera Bradley Foundation Scholar who is the first author of the publication.
Lung cancer is the deadliest cancer in the United States and around the world. Many of the currently available therapies have been ineffective, leaving patients with very few options. A promising new strategy to treat cancer has been bacterial therapy, but while this treatment modality has quickly progressed from laboratory experiments to clinical trials in the last five years, the most effective treatment for certain types of cancers may be in combination with other drugs.
Columbia Engineering researchers report that they have developed a preclinical evaluation pipeline for characterization of bacterial therapies in lung cancer models. Their new study, published December 13, 2022, by Scientific Reports, combines bacterial therapies with other modalities of treatment to improve treatment efficacy without any additional toxicity. This new approach was able to rapidly characterize bacterial therapies and successfully integrate them with current targeted therapies for lung cancer.
"We envision a fast and selective expansion of our pipeline to improve treatment efficacy and safety for solid tumors," said first author Dhruba Deb, an associate research scientist who studies the effect of bacterial toxins on lung cancer in Professor Tal Danino's lab in Biomedical Engineering, "As someone who has lost loved ones to cancer, I would like to see this strategy move from the bench to bedside in the future."
The team used RNA sequencing to discover how cancer cells were responding to bacteria at the cellular and molecular levels. They built a hypothesis on which molecular pathways of cancer cells were helping the cells to be resistant to the bacteria therapy. To test their hypothesis, the researchers blocked these pathways with current cancer drugs and showed that combining the drugs with bacterial toxins is more effective in eliminating lung cancer cells. They validated the combination of bacteria therapy with an AKT-inhibitor as an example in mouse models of lung cancer.
LONDON — The U.K. government on Friday announced a partnership with German firm BioNTech
to test potential vaccines for cancer and other diseases, as campaigners warned any breakthrough must remain affordable and accessible.
Cancer patients in England will get early access to trials involving personalized mRNA therapies, including cancer vaccines, which aim to spur the immune system to attack harmful cells.
They will be administered to early and late-stage patients and target both active cancer cells and preventing their return.
BioNTech will set up new research and development centers in the U.K., with a lab in Cambridge and headquarters in London, and aim to deliver 10,000 therapies to patients from September 2023 until the end of the decade.
The company developed one of the most widely-distributed Covid-19 vaccines alongside U.S. pharma firm Pfizer
. Its CEO, Ugur Sahin, said it had learned lessons from the coronavirus pandemic about collaboration between the British National Health Service, academics, regulators and the private sector in the development of drugs that it was applying now.
Afamitresgene autoleucel (afami-cel; formerly ADP-A2M4), an adoptive T cell receptor (TCR) therapy targeting the MAGE-A4 cancer antigen, achieved clinically significant results for patients with multiple solid tumor types in a Phase I clinical trial led by researchers at The University of Texas MD Anderson Cancer Center.
The outcomes, published today in Nature Medicine, were especially noteworthy in the subgroup of patients with synovial sarcoma, where afami-cel achieved an objective response rate of 44% compared to the overall response rate of 24% across all cancer types. Initial data from this trial were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.
According to principal investigator David S. Hong, M.D., professor of Investigational Cancer Therapeutics, these early results demonstrate a proof-of-concept for this novel cell therapy approach in solid tumors.
"These high response rates are significant because patients with synovial sarcoma really have very few options after high-dose chemotherapy with ifosfamide," Hong said. "The overall toxicity from afami-cel was manageable, and we saw evidence of early activity in other cancer types. These results suggest this is an approach with the potential to work in solid tumors where there are currently no approved cellular therapies."
Error-correcting mechanisms are very important for cells, because with all the cellular activity constantly going on, malfunctions arise all the time. But when it comes to killing cancer cells, it is in the cells' best interest to induce errors. Radiotherapy and chemotherapy can cause cellular defects by breaking the DNA of the cells. However, some tumor cells have an exceptionally efficient DNA repair machinery that allows them to evade cancer treatment.
In a paper published in Cell Reports, Óscar Llorca of the CNIO, Fernando Moreno-Herrero of the CNB and Puri Fortes of the CIMA-University of Navarra have now revealed the workings of one of these extraordinary repair systems: a molecular staple that has been shown in action for the first time using a new nanotechnology technique.
Lung cancer claims more lives each year than any other type of cancer worldwide. According to the World Health Organization, an estimated 1.8 million people died of lung cancer in 2020. Current treatments rely on one of two avenues: generalized chemotherapy that inflicts harsh side effects on cancer patients, or targeting of tumors with very specific mutations that may not apply to many patients—both of which make fighting the disease challenging.
Researchers at SRI International have designed and optimized a new peptide—a molecule that contains two or more amino acids—to act as a delivery vehicle for drugs to treat non-small cell lung cancer, which accounts for the majority of lung cancer cases. This peptide, highlighted in a recent study published in Nature Communications Biology, can carry large anti-cancer drugs and successfully target cancerous cells, binding to them and triggering a process to draw the peptide and its cargo inside.
"With our peptides, we can start to deliver large cargos inside of a cell that couldn't otherwise pass through the cell membrane," said Kathlynn Brown, vice president of drug delivery systems at SRI's Bioscience division and lead author on the paper. "It opens the door to basically dragging therapeutics into the inner workings of tumor cells while avoiding healthy cells, minimizing the potential side effects."
Currently, most similarly targeted cancer drugs are delivered by antibodies, which bind to specific receptors on the surface of a cancer cell. But there are several advantages to using peptides instead of antibodies. First, peptides are significantly smaller molecules, which means that they can penetrate deeper into a tumor. Second, peptides can be put together chemically, while antibodies must be produced biologically in cells. The chemical process is faster, less expensive and gives researchers more precise control over the final result.
"Because we make them chemically, we have a lot of flexibility in how we incorporate the drug," Brown said. "We can put on whatever drug or cargo we want, we will know exactly where it is, and we can modify that with tools we have in the lab."
To find a peptide with the right set of traits, Brown and her colleagues use a proprietary selection process to sift through a library of billions of potential options. In this case, they needed a peptide that could successfully seek out and bind to cancer cells while leaving healthy cells alone; could trigger biological processes to rapidly draw the peptide and its cargo into the cell; and wouldn't degrade while circulating through the body.
In a paper published in PNAS, Maureen Murphy, Ph.D., Deputy Director of Wistar's Ellen and Ronald Caplan Cancer Center and Ira Brind Professor and Program Leader in the Molecular & Cellular Oncogenesis Program, and team have identified a gene signature that accurately predicts the functioning of P53 variants, important information to assessing cancer risk and optimizing choices for cancer therapeutics.
"There are so many genetic variants of P53," explained Murphy. "A lot of P53 variants are classified as having uncertain significance with current methods of testing. This does not help people determine whether they have increased cancer risk. The signature we identified does."
The Murphy lab monitored differences in activity in mutant and normal p53 proteins to determine any genetic markers that would flag if a p53 variant is functioning less than normal. In collaboration with Andrew Kossenkov, Ph.D., assistant professor in Wistar's Vaccine and Immunotherapy Center, the research team used machine learning to identify a gene signature that consistently and accurately predicted the difference between a normal functioning or benign p53 and a lower functioning variant of the protein.
New QIMR Berghofer research has found that low-dose aspirin may improve ovarian cancer survival.
The study followed more than 900 Australian women newly-diagnosed with ovarian cancer, and asked them how often they used nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin.
Lead researcher Dr. Azam Majidi said the women who reported taking NSAIDs at least four days a week in the 12 months after diagnosis, lived longer on average than occasional or non-users. Most of the frequent users were taking daily low-dose aspirin.
"Our findings suggest that frequent NSAID use might improve survival for women with ovarian cancer, regardless of whether they start taking the drugs before or after diagnosis," Dr. Majidi said.
"We found the difference would translate to an average of an extra 2.5 months' survival in the five years post-diagnosis. While this might not sound like a lot, it is significant for ovarian cancer. The disease is often diagnosed at an advanced stage when the prognosis is poor, and treatment options are limited."
Scientists have revealed details of the discovery of new inhibitors of the BCL6 protein, which is involved in driving several cancer types including the blood cancer B-cell lymphoma.
The inhibitors are small molecules that block BCL6's action. With further research they could be developed into drugs to treat a range of cancer types, including blood cancers and solid tumors.
The compounds were discovered by researchers at The Institute of Cancer Research, London, through a multidisciplinary collaboration between assay scientists, medicinal chemists, biophysicists, structural biologists and other scientists at the Center for Cancer Drug Discovery at the ICR.
New adoptive T cell therapies—in which T cells, the immune system's natural hunters patrolling the body for foreign adversaries, are retrieved from cancer-riddled patients, super-charged and amplified outside the body, and then infused back into the same patient—are changing the prospects of cancer patients.
Since 2017, when CAR (chimeric antigen receptor)-T cells were green-lighted as the first modified therapeutic cells by the Federal Drug Administration (FDA) to treat leukemia, five similar products have since been approved and more than 20,000 people have been treated with this game-changing immunotherapy.
CAR-T cells are engineered to carry synthetic membrane-spanning receptor molecules that use their outside-facing portion to bind to antigens on cancer cells, which their inside-facing portion responds to by switching on a powerful tumor cell-destroying program. However, not all patients respond equally well to CAR-T cell therapies, and cancer immunologists have been trying to figure out what makes them work well or fail.
Despite a budding understanding of differences between cancer patients' T cells and healthy individuals' T cells, these insights have not been taken into account in CAR-T cell manufacturing processes. All processes use a similar type of stimulation with T-cell specific agonists and general immune-stimulating cytokines to create infusible CAR-T cell products, irrespective of variations in the original T cells' phenotype.
these types of reports frustrate me because that look at people and assume that dietary patterns are causative in the pattern of disease.
