Study reveals cost-effective means for generating more potent CAR T-cells to treat solid tumors

An innovative study led by Megan Wyatt, MS, and her translational researcher teams in the laboratories of Chrystal Paulos, PhD, and Gregory Lesinski, PhD, MPH, at Winship Cancer Institute of Emory University has uncovered a simplified, economical manufacturing process for generating more potent and metabolically fit human T-cell therapies to treat solid tumors.

This cellular therapy uses immune cells called T-cells, a type of white blood cell, taken from the patient’s blood, changed in the laboratory by adding a gene for a chimeric antigen receptor (CAR) that recognizes tumor antigen. This strategy enables the T-cells to selectively target and attack cancer after they are given back to the patient.

Dr. Paulos is a faculty member in the CB and IMP programs and Dr. Lesinski is a CB faculty member.

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Winship Cancer researchers win grant to explore new breast cancer therapy

Winship Cancer Institute researchers, led by Emory radiation oncologists Zachary S. Buchwald and David S. Yu, received a three-year, $1.2 million Breast Cancer Research Program Breakthrough Award from the U.S. Department of Defense to advance a novel approach for treating breast cancer, the most commonly diagnosed non-skin cancer in women and the second leading cause of cancer death in women in the United States.

SAMHD1, a protein that has emerged as a promising target of cancer therapy, is overexpressed in up to 27% of breast cancers, and its high expression is associated with poor outcomes in patients. The research team has developed an innovative strategy for targeting SAMHD1 in breast cancer tumors, using a natural viral accessory protein called Vpx. They plan to package Vpx in virus-like particles and use it against SAMHD1 to stimulate stem cell-like CD8+ T cells and overcome resistance to immune therapy.

The research will use human breast cancer patient samples and breast cancer mouse models to learn how SAMHD1 directs the dynamics underlying anti-tumor immunity in breast cancer and the role of SAMHD1 as a biomarker for selecting breast cancer patients who may benefit from immune therapy. The completed project will establish proof-of-concept for using virus-like particles containing Vpx to target SAMHD1, with the goal of making breast cancer immune therapy a more effective treatment strategy for a greater number of patients with breast cancer.

Dr. Buchwald is a CB faculty member and Dr. Yu is a faculty member in the CB and GMB programs.

Winship Cancer Institute researchers win grant to develop new personalized vaccine immunotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck

Immune checkpoint inhibitors are a form of cancer therapy that work by blocking proteins that keep immune responses from being too strong and stop the immune system from attacking the cancer cells. Though these therapies have improved the survival rate of patients with head and neck cancer, only a subset of patients respond to them because of the high degree of patient-to-patient variation in individual tumors.

Winship Cancer Institute researchers led by Dong Moon Shin, MD, professor of hematology and medical oncology, and Periasamy Selvaraj, PhD, professor of pathology and laboratory medicine, received a new $625,000 grant from the National Cancer Institute to help address this problem.

The five-year R01 award will support the development of a novel, personalized vaccine immunotherapy to enable more patients with head and neck cancer to benefit from immune checkpoint therapies.

The treatment will use membrane vesicles derived from a patient’s own tumor that have been modified to express immune-stimulating molecules, which will then be administered alone and together with an immune checkpoint inhibitor to boost the patient’s immune response against cancer cells.

Notably, the process does not require the establishment of cell lines, identification of tumor antigens or in vitro manipulation of immune cells, making it more cost-effective than other approaches.

The vaccine will first be evaluated in a mouse model, and if successful, will advance to a phase 1b dose-escalation clinical trial.

Dr. Selvaraj is a faculty member in the CB and IMP programs.

Veronica Canarte named one of the 2023 Edward A. Bouchet Graduate Honor Society Scholars

The National Edward Alexander Bouchet Graduate Honor Society is named for the first African American doctoral recipient in the United States, Dr. Edward Alexander Bouchet (Physics, Yale University, 1876). The Society honors outstanding scholarly achievement and promotes diversity and excellence in doctoral education and the professoriate. Inductees at Emory are doctoral and postdoctoral scholars who are committed to contributing to the development of their field(s) of study and to the application of that knowledge into action to improve the lives and conditions of the community. Members exhibit the highest values of Emory University—through their integrity, honor, and exemplary conduct and behavior.

Veronica Canarte is a Ph.D. candidate in the Cancer Biology Graduate Program at Emory University studying the role of CD28 and CD86 signaling in the survival of multiple myeloma. As an incoming graduate student, Veronica was awarded the Centennial Scholars Fellowship as an application who demonstrated outstanding academic achievement and who will contribute to the development of a richly diverse student body. Before joining Emory University, Veronica spent two years in the NIH-funded post-baccalaureate research program (PREP) at Tufts University School of Medicine studying Human papillomavirus-associated cervical cancers.

In 2018, Veronica graduated from Towson University with a B.S. in Cell and Molecular Biology where she participated in various outreach organizations while on campus. She currently resides as the Division Student Advisory Council (DSAC) representative for the Cancer Biology program advocating on behalf of students and working with the administration to address student concerns. She is also an executive member of the Latinx Graduate Student Association where she spends time fostering a community for Latinx students across Emory University’s graduate programs.

Veronica strongly believes in contextualizing social and political ramifications with some of the health consequences we see in the cancer biology field today. Ultimately, she aspires to redistribute her access to the academy and extend opportunities that contribute to prosperity and restoration of health standards in minority communities.

Congratulations to Kelsey Bennion on her F99 score!

In March 2023, Kelsey Bennion, a doctoral student in the lab of Mandy Ford, PhD, has received a perfect score (10) on a National Cancer Institute F99/K00 “Individual Predoctoral to Postdoctoral Fellow Transition Award” application. The purpose of the award is to encourage and retain outstanding graduate students who have demonstrated potential and interest in pursuing careers as independent researchers. The initial F99 phase will support Bennion’s PhD dissertation research training, which is focused on identifying novel memory T cell co-inhibitory axes that could be therapeutically targeted in cancer immunotherapy. “Kelsey has worked incredibly hard and already made important contributions in understanding regulation of tumor-specific T cell responses,” says Dr. Ford. The K00 phase will support Bennion’s postdoctoral training and career development activities relevant to her long-term goal of becoming an independent cancer researcher. Says Kelsey, “I think this unique grant mechanism through the NCI is incredibly helpful in supporting young investigators as we transition to postdoctoral research. I am grateful for my training thus far and excited for what the scientific future holds!”

Targeting galectin-9 in obesity-related chemoresistance

Researchers studying the impact of obesity on leukemia have identified galectin-9 as an important immunotherapeutic target to overcome obesity-induced chemoresistance, publishing their findings in Nature Communications. CB faculty member Curtis J. Henry, assistant professor of pediatrics and an investigator with the Aflac Cancer and Blood Disorders Center and Winship Cancer Institute of Emory University, is the study’s senior author.

Galectin-9 is a protein expressed on the surface of leukemia cells that promotes chemoresistance, and adipocytes secrete factors that promote greater levels of galectin-9. Antibody-mediated targeting of galectin-9 can significantly extend the survival of obese but not lean mice with aggressive B-acute lymphoblastic leukemia, the authors report.

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