Studies led by Wayne State University School of Medicine scientists seeking greater translational relevance in immunotherapy of pancreatic and ovarian cancers are gaining attention following 12 invited appearances at several surgical conferences, including two in two months.
WSU graduate student Oksana Gruzdyn presented findings from the laboratory of principal investigator Ramesh Batchu, Ph.D., at conferences in March and April. The lab’s overall goal is to design effective therapeutic cancer vaccines for pancreatic and ovarian cancers. The Batchu lab is located in the John D. Dingell Veterans Affairs Medical Center, and is guided by the Michael and Marian Illitch Department of Surgery Chair and Professor Donald Weaver, M.D., and VA Chief of Staff and Professor of Surgery Scott Gruber, M.D., Ph.D.
“Very few basic science abstracts are accepted in these surgical conferences, and our laboratory has been consistently presenting in various international conferences,” said Dr. Batchu, an associate professor of Surgery and director of the Division of Surgical Oncology and Developmental Therapeutics.
Gruzdyn presented the talk “Pancreatic cancer-induced microenvironment inhibits dendritic cell activation via decreased nuclear localization of NF-kB” at the Central Surgical Association’s Annual Meeting March 10-12 in Montreal.
The abstract addresses the clinically-important problem of poor outcomes in pancreatic cancer patients. Pancreatic cancer is relatively resistant to chemotherapy, providing the rationale for introducing other treatment modalities such as dendritic cell (DC)-based immunotherapy, Dr. Batchu said. Prior immunotherapeutic strategies have shown limited clinical responses due in large part to the immunosuppressive tumor microenvironment. NF-kB is a natural part of the immune defense that provides survival signals for DCs and various responder cells.
“We have examined the NF-kB pathway in the pancreatic cancer-induced microenvironment in order to delineate strategies for restoring immuno-competence, thereby enhancing cancer cell killing. Knowledge of this NF-kB pathway may prove useful in the subsequent design of DC immunotherapeutic protocols to counter the immunosuppressive nature of the tumor microenvironment,” he said.
Gruzdyn also presented “Efficient lysis of pancreatic cancer cells by MAGE-A3-Induced cytotoxic T lymphocytes using cell-penetrating peptides” at the Association of VA Surgeons Annual Meeting April 9-12 in Virginia Beach, Va.
“Dendritic cell, or DC-based, cancer vaccines can be prepared with relative ease, and have been shown to induce therapeutic anti-tumor immune responses,” Dr. Batchu said. “However, DC vaccination protocols are clearly not yet optimized, and the generation of more effective regimens continues to be an area of active research. One of the key hurdles in developing an effective DC vaccine is poor access of tumor-specific antigen, or TSA, to the intracellular HLA molecules required to generate tumor-reactive cytotoxic T lymphocytes, or CTLs. MAGE-A3, a TSA, is expressed in a significant proportion of pancreatic cancers and is associated with a poor prognosis.”
They previously described two methods to overcome the barrier by facilitating intracellular entry of the widely-expressed TSA MAGE-A3. The first method was published in JAMA Surgery in 2014, and the second in the journal Vaccine, also in 2014.
“In this study, we extended this prior work and demonstrated that DCs pulsed with MAGE-A3 linked to CPP elicit more effective anti-tumor CTL responses. CPP-MAGE-A3-DC immunotherapy, either alone or in combination with other immune-enhancing protocols, may prove useful in the clinical setting for management of pancreatic cancer,” Dr. Batchu added.
Gruzdyn won first place for a similar presentation at the WSU Department of Surgery’s annual David Fromm Research and Wayne State Surgical Alumni Day on Jan. 28.