This article is more than 5 years old. Information may no longer be current.
Personalized vaccines provoke antitumor activity in melanoma
Click Here to Manage Email Alerts
A dendritic cell vaccine targeted at patient-specific neoantigens expanded the antitumor immune response in patients with melanoma, according to study results.
“Neoantigens are like flags on a cancer cell, calling attention to the immune system,” Beatriz M. Carreno, PhD, of the division of oncology at Washington University School of Medicine, said during a press conference. “In any one patient with melanoma, there can be hundreds of flags on tumors. The challenge presented to us was how to identify the unique flags that were more likely to elicit a strong immune response against the tumor.”
Tumor missense mutations may produce antigens that the immune system perceives as foreign, which can elicit tumor-specific T-cell immunity. Researchers, thus, sought to examine the immunogenicity of tumor-encoded amino acid substitutions, according to study background.
Carreno and colleagues evaluated data from three patients with stage IIIC resected cutaneous melanoma. Two of the three patients were men and the median age was 52 years (range, 47-54). All three patients had undergone prior treatment with ipilimumab (Yervoy, Bristol-Myers Squibb).
Patients underwent genomic sequencing of their tumors and healthy tissues to identify neoantigens specific to their tumors. Researchers selected seven amino acid substitution peptide candidates for incorporation into a personalized vaccine formula, in addition to the gp100-derived peptides G209-2M and G280-9V as controls.
“This is about as personalized as vaccines can get,” study researcher Elaine Mardis, PhD, co-director of the McDonnell Genome Institute at Washington University, said in a press release. “The approach we describe is fundamentally different from conventional mutation discovery, which focuses on identifying mutated genes that drive cancer development. Instead, we’re looking for a unique set of mutated proteins in a patient’s tumor that would be most likely to be recognized by the immune system as foreign.”
Elaine Mardis
Researchers examined patients’ peripheral blood mononuclear cells before vaccination and every week thereafter to evaluate T-cell immunity in response to the vaccine.
All patients demonstrated immunity to at least one neoantigen in prevaccination samples. After treatment, vaccination yielded new immunity to additional neoantigens and enhanced previously existing neoantigen immunity. Each patient displayed vaccine-induced tumor cell immunity to two additional neoantigens.
Robust neoantigen tumor cell immunity was observed as early as the second week of treatment and peaked at weeks 8 to 9, researchers wrote.
“Immunity to multiple tumor neoantigens is an important component to any therapeutic strategy, since a diverse response might exert pressure to reduce tumors from escaping the immune system’s control,” Carreno said. “Vaccination promotes a highly diverse repertoire of neoantigen-specific tumor cells, suggesting cancer patients have a potentially rich pool of naive tumor-specific T cells, which remain dormant unless activated by vaccination.”
The researchers reported the vaccine appeared safe, and no autoimmune adverse events occurred.
“Our team has developed a new strategy for personalized cancer immunotherapy,” Gerald Linette, MD, PhD, study researcher and a medical oncologist at Washington University, said in a press release. “Many researchers have hypothesized that it would be possible to use neoantigens to broadly activate the human immune system, but we didn’t know that for sure until now. We still have much more work to do, but this is an important first step and opens the door to personalized immune-based cancer treatments.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts