A phase I vaccine trial of a HER-2/neu peptide incorporated into PLG microspheres in patients with advanced stage HER2-expressing cancers

Abstract

2572 Background: Standard methods for immunization with peptides to elicit cytotoxic T lymphocytes (CTL) have not been well defined. Injection of soluble antigens in most standard vaccine formulations induce helper T cell and antibody responses, but generally fail to elicit CTL. Preclinical studies have shown that peptides incorporated into Poly-lactide-co-glycolide (PLG) microspheres are more effective in eliciting CTL than soluble peptides. Additionally, studies in HLA-A2 transgenic mice have shown GM-CSF and monophosphoryl lipid A (MPL-AF) to be effective adjuvants for induction of CTL with PLG peptide. A Phase I vaccine study was conducted to evaluate the safety and immunogenicity of HER2 peptide p369–377 incorporated in PLG microspheres in combination with GM-CSF or MPL-AF as adjuvant in patients with advanced stage HER2 overexpressing cancers. Methods: Twenty-four HLA-A2+ patients with stage III/IV breast, ovarian, or non-small cell lung cancer were enrolled sequentially into 4 treatment arms (6 patients/arm) and received escalating doses of the vaccine (Arms 1 and 2 received 0.5 mg of HER2 peptide; Arms 3 and 4 received 1.5 mg HER2 peptide) with different adjuvants (Arms 1, 2 and 3 received GM-CSF; Arm 4 received MPL-AF) and by different administration routes (Arm 1 received intradermal injection; Arms 2, 3, and 4 received subcutaneous injection). Vaccines were administered every 28 days for a total of 6 immunizations. Toxicity assessments were conducted at baseline, prior to each vaccine and at follow-up. Immunologic responses were evaluated with IFN-γ ELIspot assay. Results: Fourteen subjects completed all 6 vaccinations. 7 patients withdrew from study because of disease progression. No serious or grade 4 toxicity related to vaccine occurred. Eighteen of 24 subjects were evaluable for immunologic responses. 11/18 subjects (61%) developed a p369–377-specific CTL response. Immune responses did not appear to be related to treatment arm. Conclusions: The HER2 p369–377/PLG vaccine plus adjuvant is safe and elicits HER2-specific T cells in patients with HER2 positive cancers. No significant financial relationships to disclose.