Researchers at the Johns Hopkins University Kimmel Cancer Center have developed a vaccine that “reprograms” pancreatic tumor cells to mount an immune response against the tumor, according to a university press release.
In their study, published in Cancer Immunology Research, researchers evaluated the vaccine in 39 patients with pancreatic ductal adenocarcinomas.
The vaccine — GVAX — utilizes tumor cells treated with irradiation. These cells are modified to effectively recruit anticancer T cells to the patient’s tumor. The investigators tested GVAX in tandem with cyclophosphamide. This “reprogramming” of tumor cells is aimed at rendering the tumors susceptible to other immune modulating drugs, according to researcher Elizabeth Jaffee, MD, the Dana and Albert “Cubby” Broccoli professor of oncology at the Johns Hopkins University School of Medicine.
Researchers found that GVAX gave rise to structures known as tertiary lymphoid aggregates within the pancreatic tumors. These structures, seen in 33 of the 39 patients who received the vaccine, facilitate the activation and response of immune cells. The aggregates were well organized and atypical of such tumors, according to study researcher Lei Zheng, MD, an assistant professor of oncology and surgery at the Johns Hopkins University School of Medicine.
“This suggests that there has been significant reprogramming of lymphocyte structures within the tumor,” Zheng said in the press release.
By activating immune cells and suppressing regulatory T cells (Tregs), such structures could alter the environment of a tumor in favor of fighting the cancer, according to Jaffee.
She said these aggregates could “really shift the immunologic balance within a tumor, setting up an environment to activate good T cells to fight the cancer, by tamping down Tregs.”
The researchers said they hope that this reprogramming technology also can be used to combat other types of cancer by optimizing tumor responses to immunotherapy. The research team will next investigate a combination of GVAX and an antibody to PD-1 in patients with pancreatic ductal adenocarcinomas.
“We think combinations of immune therapies will have the biggest impact,” Zheng said in the press release.
Disclosure: One of the researchers reports receiving commercial research support from Bristol-Myers Squibb.