Evaluation of a new oil adjuvant for use in peptide‐based cancer vaccination

Abstract

Vaccine therapies are increasingly being used for the treatment of various diseases, and the antigen molecules themselves are being expanded from whole microorganisms to fine molecules such as peptides. Accordingly, there is a need for new adjuvants to support these new applications. In this paper, we used pharmaceutical grade mineral oil and sorbitan monooleate to develop a new oil adjuvant formula, NH 2 , and investigated its effects on peptide vaccination at both the pre-clinical and clinical levels. The adjuvant effect of NH 2 on peptide-induced cellular immunity in mice was superior to that of Montanide ISA51VG, a commercially available incomplete Freund's adjuvant for clinical use, although no significant difference was observed between the two adjuvants on peptide-induced humoral immunity. The adjuvant effects of NH 2 were also confirmed in a Phase-I clinical trial of peptide vaccines for patients with advanced cancers. These results suggest that NH 2 is a suitable adjuvant for peptide vaccination, particularly for cancer vaccines (Phase-I clinical trial of pan-HLA type personalized peptide vaccine for advanced cancer patients, UMIN clinical trial registry number: UMIN 000000619). (Cancer Sci 2010; 101: 2110-2114 V accine therapies have long been used for the prevention of infectious diseases. However, recent advances in immunology and molecular pathology have led to the use of vaccines not only for the prevention but also for the treatment of allergies, (1,2) autoimmune diseases, (3)(4)(5) cancer, (6,7) Alzheimer disease, (8) and hypertension. (9) At the same time, the antigens in the vaccine formulas have expanded from whole microorganisms to fine molecules such as epitope peptides. There is, thus, a need for new adjuvants to be used in these new applications.Incomplete Freund's adjuvant (IFA) is one of the most famous adjuvants and is widely used for protein and peptide antigens to induce both humoral and cellular immunity in animals and humans. There are currently only two IFA formulas commercially available for clinical use: Montanide ISA51(VG) and ISA720 (products of Seppic, Paris, France).(10,11) Both Montanide ISA51(VG) and the original formula of IFA, consist of mineral oil and mannide monooleate.(10) Although pharmaceutical-grade (i.e. meeting the requirements of pharmacopeia such as the Japanese pharmacopeia and US pharmacopeia) mineral oil is commercially available, pharmaceutical-grade formulas of mannide monooleate, such as Montanide 80 (Seppic), are difficult to obtain, particularly for academic researchers. A highpurity oleic acid derivative, sorbitan monooleate (NOFABLE SO-991), has recently been made available, and its regulatory status meets the requirements of the Japanese pharmaceutical excipients. Therefore, we attempted to develop a new oil adjuvant formula for clinical use using a pharmaceutical grade mineral oil and sorbitan monooleate. In this paper, we investigated the effects of the new adjuvant on peptide vaccination at both the pre-clinical and clinical levels. Materials and ...

TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC

“…12 Tat-interacting protein of 110 kDa (TIP110), which was initially cloned from a human KG-1 myeloid cell line cDNA library, 13 is implicated in RNA metabolism and tumor-antigen presentation. [14][15][16][17] We demonstrated previously that TIP110 regulates the transcription of HIV-1 and cellular genes. 18,19 It is considered a mammalian homolog of the yeast Prp24 protein, and functions as a general pre-mRNA splicing factor.…”

Recent progress in adjuvant discovery for peptide-based subunit vaccines

“…NH 2 was extensively used as an adjuvant for peptide-based cancer vaccination and outperformed Montanide ISA 51 in the induction of a cellular immune response in mice. 44 The efficacy of the peptide-based vaccine adjuvanted by NH 2 was confirmed in phase-1 clinical trials with advanced cancer patients.…”

Peptide Vaccine: Progress and Challenges

“…Various other modifications of existing emulsion based delivery systems have promising future, e.g., NH 2 containing mineral oil and high purity oleic acid derivative, sorbitan monooleate. NH 2 being a w/o emulsion was able to protect encapsulated peptide antigen from peptidase and also provided a slow release of the peptide giving sustained antigenic stimulation [ 70 ]. Similarly a novel w/o/o multiple emulsion system containing squalene oil encapsulating peptide antigen gp100 was investigated for its efficacy as a vaccine delivery system for melanoma immunotherapy [ 64 ].…”

“…Also, they elicited CTL response in presence of CPG (added as an adjuvant) and inhibited the growth of tumors in mice [ 72 , 73 ]. Induction of CTL response was also observed in liposomes surface decorated with peptides derived from a non-structural polyprotein in severe acute respiratory syndrome (SARS)-associated coronavirus [ 70 , 74 ]. In a similar study, hepatitis C virus derived peptides coupled to surface of liposomes were found to confer complete protection to immunized mice with the establishment of long term memory [ 72 , 75 ].…”