Abstract Title

Th1 cytokines sensitize human pancreatic cancer cell lines to treatment with Lapatinib

Abstract

In 2018 approximately 56,000 people in the United States will be diagnosed with pancreatic cancer. Prognosis is dismal, with a 5-year survival rate of only 7% making this cancer the 2ndleading cause of cancer-related deaths in the United States. Despite advances in chemo-, radiation and surgical therapies, survival rates have not improved in over 40 years. Alternative treatment options therefore need to be explored to improve outcomes. Immunotherapy is emerging as viable option to traditional cancer treatments. A recent clinical trial to treat early breast cancer showed great promise by using autologous dendritic cells to promote activity of T lymphocytes of the “Th1”helper phenotype, and directing them against a tumor-associated protein called HER-2. These Th1 cells appear to work in part by producing soluble factors called cytokines, including Interferon-gamma and TNF-alpha. These cytokines have been shown to induce programmed cell death (apoptosis) in the breast cancer cell lines. We thus hypothesized that a similar vaccine approach may work for pancreatic cancer, which can also express HER-2 and other HER-family proteins. To leverage the anti-cancer effect of vaccination, we are also exploring the addition of targeted drugs including the HER-family antagonist, lapatinib. Using a variety of in vitro techniques, we show that Th1 cytokines in combination with lapatinib work togeter in vitro to maximize markers of apoptotic cell death in several human pancratic cell lines. These studies represent pre-clinical data suggesting the exploration of Th1-polarizing vaccines and small molecule inhibitors in clinical vaccine trials for pancreatic cancer.

Modified Abstract

Pancreatic cancer is the second-leading cause of cancer related deaths with a dismal 5-year survival rate of 7%. We are therefore seeking alternate and improved therapeutic modalities. Recent trials using an experimental vaccine for early breast cancer has shown promising results, and important effectors of vaccine-induced immunity appear to be soluble immune system factors IFN-γ and TNF-α which cause apoptotic cell death in breast cancer cells. In order to test the feasibility of deploying a similar vaccine for pancreatic cancer, we have tested the sensitivity of a panel of human pancratic cancer cell lines to these cytokines plus a small molecule inhibitor of HER-family oncodrivers, lapatinib. The combination maximized markers of apoptotic cell death suggesting this is a feasable approach.

Research Category

Biomedical Sciences

Primary Author's Major

Biology

Mentor #1 Information

Dr. Gary

Koski

Mentor #2 Information

Dr. Lori

Showalter

Mentor #3 Information

Mr. Chase

Steele

Presentation Format

Poster

Start Date

April 2019

Research Area

Allergy and Immunology | Cancer Biology | Immunity | Oncology

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Apr 9th, 1:00 PM

Th1 cytokines sensitize human pancreatic cancer cell lines to treatment with Lapatinib

In 2018 approximately 56,000 people in the United States will be diagnosed with pancreatic cancer. Prognosis is dismal, with a 5-year survival rate of only 7% making this cancer the 2ndleading cause of cancer-related deaths in the United States. Despite advances in chemo-, radiation and surgical therapies, survival rates have not improved in over 40 years. Alternative treatment options therefore need to be explored to improve outcomes. Immunotherapy is emerging as viable option to traditional cancer treatments. A recent clinical trial to treat early breast cancer showed great promise by using autologous dendritic cells to promote activity of T lymphocytes of the “Th1”helper phenotype, and directing them against a tumor-associated protein called HER-2. These Th1 cells appear to work in part by producing soluble factors called cytokines, including Interferon-gamma and TNF-alpha. These cytokines have been shown to induce programmed cell death (apoptosis) in the breast cancer cell lines. We thus hypothesized that a similar vaccine approach may work for pancreatic cancer, which can also express HER-2 and other HER-family proteins. To leverage the anti-cancer effect of vaccination, we are also exploring the addition of targeted drugs including the HER-family antagonist, lapatinib. Using a variety of in vitro techniques, we show that Th1 cytokines in combination with lapatinib work togeter in vitro to maximize markers of apoptotic cell death in several human pancratic cell lines. These studies represent pre-clinical data suggesting the exploration of Th1-polarizing vaccines and small molecule inhibitors in clinical vaccine trials for pancreatic cancer.