City of Hope® Researchers will present more than 70 abstracts and sessions on groundbreaking clinical trial results, innovative diagnostic techniques, and advances in treatment options, as well as share their expertise on molecular profiling and the microbiome, at the AACR Annual Meeting, which began on April 5 and ends in April. 10 in San Diego.
In addition to the strong City of Hope data presented throughout the meeting, Juan D. CarpinteroPh.D., chief scientific officer and distinguished chair of the director of the Irell & Manella Cancer Center and chair of the Morgan & Helen Chu director of the Beckman Research Institutewill chair and serve as featured speaker for the presentation. “Molecular profiling in breast cancer and racial/ethnic minorities: dedicated to the memory of Edith P. Mitchell” on Monday, April 8, 2024 at 10:15 a.m.
On Tuesday, April 9, 2024, from 10:15 a.m. to 11:45 a.m., Marcel van den BrinkM.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center and Deana and Steve Campbell, distinguished chief medical officer executive chair, will lead a major symposium as chair on The microbiome and response to cancer treatment. He will also present at "The role of the gut microbiome in cancer immunotherapy" discuss clinical and preclinical studies that demonstrate how changes in the gut microbiome can affect outcomes after hematopoietic cell transplantation and CAR T-cell therapy.
“City of Hope's research presented at this year's AACR conference reinforces our focus on early detection, smarter and more precise treatments, and achieving health equity. Through our national system, City of Hope continues to expand the reach and impact of our world-class, transformative scientific and clinical care to support more people living with cancer, regardless of where they are," Carpten said.
"Cancer is complex, and the breadth and diversity of this year's research further underscores the talent, scientific rigor and curiosity of City of Hope," Van den Brink added. "City of Hope is a powerhouse in cancer research and we are proud to share our expertise and present cutting-edge research on a wide range of cancer topics at the AACR."
Research highlights include:
Detection of early stage pancreatic cancer
Pancreatic cancer diagnosed once it has spread beyond the pancreas is highly untreatable: the five-year relative survival rate is only 3.2% for such patients, according to the National Cancer Institute. But those diagnosed when the cancer is contained in the pancreas have a relative survival rate of 44.3% after five years.
"Developing a test that can better detect stage 1 and 2 pancreatic cancers is crucial to improving survival rates for this devastating disease," he said. Ajay GoelPh.D., M.S., City of Hope professor and chair of the Department of Molecular Diagnostics and Experimental Therapeutics.
A City of Hope team led by Goel and Caiming Xu, Ph.D., a postdoctoral fellow in Goel's lab, developed an exome-based liquid biopsy test that detected 97% of early-stage pancreatic ductal adenocarcinomas when was combined with the biomarker CA 19.-9 in people enrolled in the study from the United States, South Korea, Japan and China. The results of the study were presented today at an AACR news conference.
Five hundred and twenty-three people with pancreatic cancer and 461 healthy donors participated in the study, including: United States (139 with pancreatic cancer, 193 healthy donors), South Korea (184 with pancreatic cancer, 86 healthy donors), Japan ( 150 with pancreatic cancer; 102 healthy donors) and China (50 with pancreatic cancer; 80 healthy donors).
Current biomarkers used in the clinic, such as the CA19-9 blood test, lack sufficient sensitivity for early detection of pancreatic cancer. Other challenges include the location of the pancreas deep in the abdomen.
To overcome these challenges, the City of Hope team increased the specificity and sensitivity of their novel liquid biopsy approach by testing plasma for exosomal cargo, which is shed by tumors and reflects their tissue of origin. The team also identified and tested eight microRNAs, which are small molecules found in exosomes secreted by pancreatic cancers. They then combined these microRNAs with five free DNA markers found in the blood of pancreatic cancer patients to develop a signature that detects this disease.
The liquid biopsy signature was first tested in the Japanese cohort and then validated in the United States, South Korea, and China cohorts. Study results show that the liquid biopsy method detected 93% of pancreatic cancers in the United States cohort, 91% of pancreatic cancers in the South Korean cohort, and 88% of pancreatic cancers in the South Korean cohort. pancreas in the Chinese cohort.
Additionally, when the researchers combined their signature with the pancreatic cancer marker CA19-9, the liquid biopsy test accurately detected 97% of stage 1-2 pancreatic cancers in the US cohort.
“The results are interesting because pancreatic cancer diagnosed after it has spread significantly is devastating and has a low survival rate. But if we catch it early, there's a better chance we can remove it surgically and treat it further,” said Goel, lead author of the study.
"Our exosome-based diagnostics detected more pancreatic cancers early, inspiring hope for earlier detection and treatment of pancreatic cancer," said Xu, the study's first author.
Based on the team's trial results, Xu said it could be offered to specific groups who are at higher risk of developing pancreatic cancers, such as people with new-onset diabetes, benign cysts, chronic pancreatitis or a family history of pancreatic cancer.
The presentation, titled "An exosome-based liquid biopsy for non-invasive early detection of patients with pancreatic ductal adenocarcinoma: a multicenter, prospective study." He will also be presented today from 4:05 to 4:20 p.m. during a session on early detection and biomarkers of progression.
The National Cancer Institute of the National Institutes of Health supported this study. Scientists at the Translational Genomics Research Institute, part of City of Hope, also contributed to the study.
Treatment of advanced cancers with an oncolytic virus
Daneng LiMD, City of Hope associate professor in the Department of Medical Oncology and Therapeutic Research, will share results from the first-in-human Phase 1 clinical trial of “CF33-hNIS oncolytic virus for the treatment of advanced cancer” in poster session on Tuesday, April 9, 2024, from 9 a.m. to 12:30 p.m.
Before the clinical trial, the Oncolytic virus developed by City of Hope It had been shown that CF33-hNIS reduce colon, lung, breast, ovarian and pancreatic cancer tumors in preclinical laboratory and animal models. Oncolytic virus therapy uses naturally occurring viruses that are genetically modified to infect, replicate and kill cancer cells while sparing healthy cells.
In collaboration with Imugene Limited, a clinical-stage immuno-oncology company that has licensed the engineered virus, researchers administered CF33-hNIS intratumorally or intravenously in adult patients with metastatic or advanced solid tumors in a Phase 1 trial. 1 dose increase.
Preliminary data from this trial demonstrate encouraging antitumor activity with CF33-hNIS treatment, Li said. In particular, one patient with cholangiocarcinoma or biliary tract cancer achieved a complete immune response, meaning disappearance of all signs of cancer after treatment with CF33-hNIS with no known recurrence after one year.
Furthermore, patients who responded to CF33-hNIS treatment showed a robust innate and adaptive immune response that promotes antitumor immunity. Further analysis of the T cell repertoire reveals that T cell diversity may serve as a predictive biomarker.
"The results show that our new oncolytic virus, alone or in combination with immunotherapy, has the ability to control several types of cancer that were previously resistant to other treatment options," Li said, noting that the treatment also turned out to be safe with effects minimal secondaries. effects at the doses tested. "These early results give patients hope for a new treatment option for cancers refractory to standard treatment."
Li said the encouraging early efficacy has prompted development of the next part of the study with expansion to several tumor types, including traditionally resistant tumors such as biliary tract cancer and others.
AI can predict colorectal cancer survival rates
Esteban GruberM.D., Ph.D., MPH, vice president of City of Hope National Medical Center, Eva and Ming Hsieh, family director chair of the Center for Precision Medicine and medical oncologist, will report findings from the work of an international team of researchers. investigating how "Artificial intelligence measures of tumor-infiltrating lymphocytes predict overall and colorectal cancer-specific survival" in poster session on Wednesday, April 10, 2024, from 9 a.m. to 12:30 p.m.
The team developed and tested a new artificial intelligence (AI)-powered deep learning model, called HopeSTIL©, that provides a highly efficient algorithm for analyzing digital pathological images of colorectal cancer. The algorithm can quickly and accurately quantify tumor-infiltrating lymphocytes (TILs), which can be used as biomarkers of treatment response and long-term prognosis in patients.
Identification of TILs typically requires a pathologist to manually count and score immune cells under a microscope. This process is difficult and tedious and therefore rarely occurs.
"HopeSTIL can recognize, identify and count immune cells accurately and efficiently without a microscope or pathologist," Gruber said, noting that the technology can also predict five-year survival and overall survival rates. "AI-predicted immune cells within the tumor are associated with improved five-year colorectal cancer-specific survival."
Gruber and team used a large data set of 1,738 colorectal cancer cases to evaluate the model's positive prediction rate and tested it on a second independent data set of 223 cases to validate its success.
"No matter if you adjust for all other characteristics that may affect survival, such as age, sex, race, ethnicity, stage, or other molecular characteristics, it is still a strong predictor of cancer-specific survival," Gruber said. "We hope to leverage this technology in the clinic so it can help us diagnose and treat colorectal cancer more accurately."
