Use of a canine melanoma vaccine in the management of malignant melanoma in an African penguin (Spheniscus demersus)

CASE DESCRIPTION A 25-year-old 4.4-kg male aquarium-hatched African penguin (Spheniscus demersus) was evaluated because of a raised 1.5 × 0.5-cm pigmented mass extending from within the right naris noted 2 days earlier. CLINICAL FINDINGS The penguin had a raised pigmented mass extending out from the right naris and onto the upper beak. Histologic examination of excisional biopsy specimens confirmed a diagnosis of malignant melanoma. A treatment plan including administration of meloxicam, radiation therapy, and immunotherapy was initiated. TREATMENT AND OUTCOME Treatment with meloxicam (0.2 mg/kg, PO, q 24 h) was initiated and continued for a total of 45 weeks; however, the medication was discontinued for a period of 6 weeks because of the risk of toxic effects in the chick that the penguin was feeding at that time. The penguin underwent local hypofractionated radiation therapy and received 4 once weekly 8-Gy fractions of radiation (total radiation dose, 32 Gy). The penguin was administered a canine melanoma vaccine transdermally every other week for 4 doses, with a booster injection given 7 months after the first dose. Treatment with the vaccine appeared to have no adverse effects. The penguin’s pre- and postvaccination tyrosinase-specific antibody titers were measured with an anti–human tyrosinase-specific ELISA, and a 3-fold titer increase indicated a positive humoral immune response to the canine melanoma vaccination. The penguin died of unrelated causes 54 weeks after initial diagnosis, and there was no evidence of metastasis on necropsy. CLINICAL RELEVANCE These case findings suggested that vaccination with a canine melanoma vaccine may be a safe and useful adjunct treatment for management of malignant melanoma in penguins.

Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence

BackgroundMost patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here.MethodsPatients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients.ResultsFor randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients <60 years old (HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)).ConclusionsSeviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas.Trial registration numberNCT01546571.

EVALUATION OF IMMUNOGENICITY OF SYNTHETIC NEOANTIGEN PEPTIDES FOR THE MELANOMA VACCINE MODEL

Introduction. Immunotherapy based on the usage of mutant tumor neoantigens to activate the antitumor immune response is one of the most promising approaches to cancer treatment.Purpose. Evaluation of individual immunogenicity of synthetic neoantigen peptides for the B16-F10 melanoma vaccine model.Materials and methods. We studied 32 synthetic neoantigen peptides with a length of 25–27 amino acids, which were previously selected as potentially immunogenic by bioinformatic analysis of B16-F10 melanoma sequencing data and healthy tissues of C57Bl/6J mice. Groups of C57Bl/6J mice were immunized four times at weekly intervals with each individual peptide in combination with the adjuvant Poly(I:C), one of the groups was immunized only with Poly(I:C), and the control group was not immunized with anything. The immunogenicity of peptides was assessed by the production of interferon γ in splenocytes using the ELISpot method and by the level of serum cytokines Th1/Th2 using the ELISA method in immunized mice and in animals in the control group.Results. Of the 32 peptides studied, 25 caused an increase in the number of interferon-γ-producing spleen cells in previously immunized mice, but 8 of these peptides caused a non-specific increase in the production of interferon γ by splenocytes in non-immunized animals. It was found that out of 32 peptides, only 11 caused an increase in the level of serum cytokines interferon γ and interleukin 4, which are responsible for the development of the immune response along the Th1 and Th2 pathways. But only 7 peptides affected an increase in the number of interferon-γ-producing splenocytes and an enhance of cytokines interferon γ and interleukin 4 levels.Conclusion. Thus, the immunogenicity of 32 synthetic neoantigen peptides was evaluated, and 7 peptides were shown to activate the cellular immune response.