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City of Hope Research Highlights at AACR 2024

City of Hope is committed to expanding access to leading-edge treatment, research and equitable cancer care to more patients and diverse communities.

Our thought leaders — under the leadership of Marcel van den Brink, M.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center and the Deana and Steve Campbell Chief Physician Executive Distinguished Chair in Honor of Alexandra Levine, M.D.,  and John Carpten, Ph.D.,  City of Hope chief scientific officer and the Irell & Manella Cancer Center Director's Distinguished Chair — delivered their latest research findings at the 2024 American Association of Cancer Research (AACR) Annual Meeting from April 5 to 10, 2024. 

Detecting Early-Stage Pancreatic Cancer

A promising new test for early-stage pancreatic ductal adenocarcinoma when combined with biomarker CA-19

Pancreatic ductal adenocarcinoma (PDAC), a highly untreatable disease, ranks among the most lethal human malignancies, with the lack of robust diagnostic markers contributing to its predominant diagnosis at advanced stages when it has spread beyond the pancreas.

Doctor Ajay Goel
Ajay Goel, Ph.D., M.S.

A City of Hope team led by Ajay Goel, Ph.D., M.S., City of Hope professor and chair of the Department of Molecular Diagnostics and Experimental Therapeutics, and Caiming Xu, Ph.D., a postdoctoral fellow in Goel’s lab, presented a multicenter and prospective study on a developing test that can better detect stage 1 and stage 2 pancreatic cancer.

To overcome challenges faced by current biomarkers currently used in the clinic, researchers elevated the specificity of their novel liquid biopsy approach by testing plasma for exosomal cargo. The team was also able to identify and test eight microRNAs and combine these microRNAs with five cell-free DNA markers found in pancreatic cancer patients’ blood to further develop a signature that would more accurately detect the disease.

The results of the study, supported by the National Cancer Institute of the National Institutes of Health, successfully established a noninvasive exome-based liquid biopsy test that detected 97% of early-stage PDAC when combined with biomarker CA 19-9 in participants enrolled in the study from the United States, South Korea, Japan and China. The results may potentially be further validated for clinical use in the near future.

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Treating Advance Cancers with an Oncolytic Virus

A first-in-human Phase 1 dose escalation study of oncolytic virus CF33-hNIS in adult patients with metastatic or advanced solid tumors (MAST)

In a poster session, Daneng Li, M.D., a City of Hope associate professor in the Department of Medical Oncology and Therapeutics Research, shared results of the first-in-human Phase 1 dose escalation trial of “Oncolytic virus CF33-hNIS for the treatment of advanced cancer.”

Daneng Li Bio
Daneng Li, M.D.

The trial was conducted in two parts and in collaboration with Imugene Limited, a clinical stage immune-oncology company that licensed the City of Hope-developed oncolytic virus. Researchers evaluated the safety of the oncolytic virus when administered intratumorally (IT) or intravenously (IV) in combination with pembrolizumab in patients with advanced or metastatic solid tumors with two or more prior lines of therapy.

Preliminary data from the trial demonstrates encouraging anti-tumor activity with CF33-hNIS treatment, demonstrating that CF33-hNIS alone or in combination with pembrolizumab is a safe treatment option for advanced cancer. Patients who responded to CF33-hNIS treatment showed robust innate and adaptive immune response that promotes anti-tumor immunity. This encouraging early efficacy has prompted the advancement to the second part of the study, with an expansion into various tumor types, including traditionally resistant tumors such as biliary tract cancers. 

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A Molecular Profiling Analysis of Colorectal Cancer in Hispanic-Latinos

A multi-omics characterization of molecular features and global-local genomic ancestry analysis of colorectal cancer in Hispanic-Latinos

Clinical factors and molecular characteristics play pivotal roles in shaping therapeutic strategies and prognoses in colorectal cancer, the second leading cause of cancer-related death in the United States. Despite an overall decline in mortality, the Hispanic/Latino population in the Los Angeles area has mortality rates in colorectal cancer up to 20% higher than their Caucasian American counterparts, often facing diagnoses at a younger age and advanced disease stages.

Enrique Velazquez Villarreal, M.D., Ph.D., M.P.H., M.S.
Enrique Velazquez Villarreal, M.D., Ph.D., M.P.H., M.S.

Led by Enrique Velazquez Villarreal, M.D., Ph.D., M.P.H., M.S., City of Hope assistant professor Department of Integrative Translational Services, and senior author John Carpten, Ph.D., chief scientific officer of the Irell & Manella Cancer Center Director’s Distinguished Chair and the Morgan & Helen Chu Director’s Chair of the Beckman Research Institute, the study explored clinical DNA and RNA sequencing data from the Hispanic-Latino population in Los Angeles. Using the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network and the Oncology Research Information Exchange Network (ORIEN), researchers conducted an integrative translational analysis of reported genomic alterations and their implications for colorectal tumorigenesis.

The results presented in a mini-symposium session demonstrated distinct age-of-onset, Amerindian (AMR) and survival patterns observed with significant mutations identified in key genes, suggesting that cancer heterogeneity was evident and influenced by mutation type, microsatellite instability, subsite and ethnicity. These findings contribute essential insights into DNA- and RNA-level characterization of colorectal cancer and serve as a cornerstone for forthcoming sample analyses within the PE-CGS project to potentially lead to the development of more personalized treatments.

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The Impact of Gut Microbiome Manipulation on PSCA-CAR T Cell Therapy in Prostate Cancer

Evaluating the impact of microbiome manipulation on gut microbe diversity, systemic immunity, local TME, and PSCA-targeted chimeric antigen receptor (CAR) T cell therapy in prostate cancer

John Murad, Ph.D., a staff scientist in the laboratory of senior author Saul J. Priceman Ph.D., City of Hope associate professor, Department of Hematology & Hematopoietic Cell Transplantation, presented a poster session on their research into the growing evidence that the responsiveness of immunotherapy is influenced by the composition of a patient’s gut microbiota.

Doctor John Murad headshot
John Murad, Ph.D.

The study, utilizing a mouse model of PCSA+ prostate cancer, sequentially modified the gut microbiome using antibiotic clearance followed by distinct human-derived fecal matter transfers (CPI-FMT, HD-FMT or No-FMT) while simultaneously treating the microbiome-modified tumor-bearing mice with PSCA-targeting CAR T cells to measure differences in anti-tumor efficacy and survival.

Results revealed that mice treated with CPI-FMT experienced an enrichment of specific microbes associated with the preservation of gut homeostasis and improved immune response. The study’s authors aim to further develop this model to interrogate candidate-targeted microbiome modifiers that may impact mechanisms promoting CAR T cell and immune function.

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Utilizing AI to Predict Colorectal Cancer Survival Rates

AI-driven deep learning model called HopeSTIL© shows promise using a highly efficient algorithm for analyzing digital pathology images of colorectal cancer

Identifying tumor infiltrating lymphocytes (TILs) per high-powered field (HPF) is a useful, independent, validated prognostic marker in colorectal cancer, typically requiring a pathologist to follow a difficult, tedious and rare process of manually counting and scoring immune cells under a microscope.

In a poster session, Medical Oncologist Stephen Gruber, M.D., Ph.D., M.P.H., vice president of City of Hope National Medical Center and Eva and Ming Hsieh Family Director’s Chair of the Center for Precision Medicine, reported findings from an international team of researchers’ work investigating how “Artificial intelligence measures of tumor infiltrating lymphocytes predict colorectal cancer-specific and overall survival.”

Stephen Gruber
Stephen Gruber, M.D., Ph.D., M.P.H.

This newly constructed AI-driven deep learning model, HopeSTIL©, provides a highly efficient algorithm for analyzing digital pathology images of hematoxylin and eosin (H&E) sections of colorectal cancer to quantify TILs per HPF and is a validated prognostic marker for five-year colorectal cancer survival and overall survival rates. To create and test this model, the team used a large dataset of 1,738 colorectal cancer cases to assess the model’s positive prediction rate and tested it in a second independent dataset of 223 cases to validate its success.

The results from this study will enable researchers to further leverage this technology in the clinic to diagnose and treat colorectal cancer more accurately.

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