Cancer Vaccine Boosted
Scientists at Thomas Jefferson University who are developing a cancer vaccine to prevent recurrences of gastric, pancreatic, esophageal, and colon cancers say they have added a component that would make the vaccine more effective. The change makes the vaccine less prone to being cleared by the immune system before it can generate immunity against the tumor components.
The preclinical studies pave the way for a Phase II clinical trial opening to patients this fall, according to Adam Snook, PhD, assistant professor in the department of pharmacology and experimental therapeutics and researcher at the NCI-Designated Sidney Kimmel Cancer Center (SKCC)—Jefferson Health.
“Our data show strong immune responses in mice that might otherwise clear the vaccine, and suggests this approach will be more effective in the human trials we are starting shortly,” he said. “Adenovirus serotype 5 (Ad5) is a commonly used viral vector for transient delivery of transgenes, primarily for vaccination against pathogen and tumor antigens. However, endemic infections with Ad5 produce virus-specific neutralizing antibodies (NAbs) that limit transgene delivery and constrain target-directed immunity following exposure to Ad5-based vaccines.
“Indeed, clinical trials have revealed the limitations that virus-specific NAbs impose on the efficacy of Ad5-based vaccines. In that context, the emerging focus on immunological approaches targeting cancer self-antigens or neoepitopes underscores the unmet therapeutic need for more efficacious vaccine vectors.
“Here, we evaluated the ability of a chimeric adenoviral vector (Ad5.F35) derived from the capsid of Ad5 and fiber of the rare adenovirus serotype 35 (Ad35) to induce immune responses to the tumor-associated antigen guanylyl cyclase C (GUCY2C).
“In the absence of pre-existing immunity to Ad5, GUCY2C-specific T-cell responses and antitumor efficacy induced by Ad5.F35 were comparable to Ad5 in a mouse model of metastatic colorectal cancer. Furthermore, like Ad5, Ad5.F35 vector expressing GUCY2C was safe and produced no toxicity in tissues with, or without, GUCY2C expression. Importantly, this chimeric vector resisted neutralization in Ad5-immunized mice and by sera collected from patients with colorectal cancer naturally exposed to Ad5.
“These data suggest that Ad5.F35-based vaccines targeting GUCY2C, or other tumor or pathogen antigens, may produce clinically relevant immune responses in more (≥90%) patients compared with Ad5-based vaccines (~50%).”