Prospects for a personalized peptide vaccine against lung cancer.

: The tumor characteristics and immunological status of the host should be carefully considered for the successful development of cancer peptide vaccines. Recently, personalized peptide vaccines (PPV) that individually select antigens for each patient are being developed for lung cancer. : Novel PPV, in which appropriate vaccine antigens are selected in each patient by assessing preexisting immunity to a panel of vaccine peptide candidates, have been attempted with promising results in early-phase clinical trials for lung cancer.

Identification of Novel HLA Class II-Restricted Neoantigens Derived from Driver Mutations.

Neoantigens derived from tumor-specific genetic mutations might be suitable targets for cancer immunotherapy because of their high immunogenicity. In the current study, we evaluated the immunogenicity of 10 driver mutations that are frequently expressed in various cancers using peripheral blood mononuclear cells from healthy donors ( = 25). Of the 10 synthetic peptides (27-mer) derived from these mutations, the six peptides from KRAS-G12D, KRAS-G12R, KRAS-G13D, NRAS-Q61R, PIK3CA-H1047R, and C-Kit-D816V induced T cell responses, suggesting that frequent driver mutations are not always less immunogenic.

Murine Splenic Natural Killer Cells Do Not Develop Immunological Memory after Re-Encounter with Mycobacterium bovis BCG.

Several lines of evidence have recently suggested that natural killer (NK) cells develop immunological memory against viral infections. However, there is no apparent evidence that NK cells acquire specific memory against Mycobacterium bovis bacillus Calmette-Guérin (BCG), the only currently licensed vaccine for preventing tuberculosis. In the present study, we investigated whether murine splenic NK cells can be activated by BCG in a dendritic cell (DC)-independent or -dependent manner, and furthermore examined whether these NK cells acquire specific memory following BCG vaccination.

A tumor lysate is an effective vaccine antigen for the stimulation of CD4(+) T-cell function and subsequent induction of antitumor immunity mediated by CD8(+) T cells.

To develop a potent cancer vaccine, it is important to study how to prepare highly immunogenic antigens and to identify the most appropriate adjuvants for the antigens. Here we show that a tumor lysate works as an effective antigen to prime CD4(+) T-cell help when baculovirus is employed as an adjuvant. When immunized intradermally with the combination (BLP) of baculovirus, a CT26 tumor lysate, and a cytotoxic T-cell epitope peptide before a tumor challenge, 60% of mice rejected tumors.

Intradermal immunization with combined baculovirus and tumor cell lysate induces effective antitumor immunity in mice.

Although tumor lysate contains all the potential helper and killer epitopes capable of stimulating T cells, it is difficult to use as a cancer vaccine because it suppresses dendritic cell (DC) function. We report that wild-type baculovirus possesses an adjuvant effect to improve the immunogenicity of tumor lysate. When mice were administered CT26 tumor cell lysate combined with baculovirus intradermally, antitumor immunity was induced and rejection of CT26 tumor growth was observed in 40% of the immunized mice.

Recombinant Mycobacterium bovis BCG vector system expressing SIV Gag protein stably and persistently induces antigen-specific humoral immune response concomitant with IFN gamma response, even at three years after immunization.

A vaccine against HIV-1 infection absolutely needs the ability to effectively elicit virus-specific immunity over a long term; nevertheless, there have been few studies indicating that the immunoinductivity of such a candidate vaccine has been researched for several years running. In a previous report, we demonstrated that recombinant BCG (rBCG) expressing the full-length gag gene of simian immunodeficiency virus (SIV) (rBCG-SIVgag) induced Gag-specific delayed-type hypersensitivity, T cell proliferation, gamma interferon (IFN gamma), and serum IgG responses in guinea pigs immunized intradermally (i.d.

Intradermal and oral immunization with recombinant Mycobacterium bovis BCG expressing the simian immunodeficiency virus Gag protein induces long-lasting, antigen-specific immune responses in guinea pigs.

To develop a new recombinant BCG (rBCG) vaccine, we constructed rBCG that expresses the full-length Gag protein of simian immunodeficiency virus (rBCG-SIVGag) at a level of 0.5 ng/mg after 3 weeks of bacterial cell culture. Intradermal (i.

Oral recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing HIV-1 antigens as a freeze-dried vaccine induces long-term, HIV-specific mucosal and systemic immunity.

Induction of HIV-1-specific immune responses was evaluated using a recombinant BCG (rBCG) vector-based vaccine expressing HIV-1 Env V3 peptide (rBCG-pSOV3J1). rBCG-pSOV3J1 was manufactured as a freeze-dried preparation based on good laboratory practice guidelines. Guinea pigs were immunized with the freeze-dried rBCG vaccine by oral administration to test the effectiveness of what is generally considered the most convenient and practical route for vaccination.

Combined intrarectal/intradermal inoculation of recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) induces enhanced immune responses against the inserted HIV-1 V3 antigen.

The development of a successful recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) vector-based vaccine for human immunodeficiency virus type 1 (HIV-1) requires the induction of high levels of HIV-1-specific immunity while at the same time maintaining immunity to tuberculosis. To examine a combined vaccination strategy for enhancement of immune responses specific for HIV-1, guinea pigs were inoculated with either a single or combination intradermal (i.d.

Dynamics of gamma interferon, interleukin-12 (IL-12), IL-10, and transforming growth factor beta mRNA expression in primary Mycobacterium bovis BCG infection in guinea pigs measured by a real-time fluorogenic reverse transcription-PCR assay.

The guinea pig has been utilized as a model for studying infectious diseases because its reactions closely resemble those of humans biologically and immunologically. However, the cytokine responses in this animal remain to be studied. Initially, we established a quantitative assay using a real-time reverse transcription-PCR (RT-PCR) to measure guinea pig gamma interferon (IFN-gamma), interleukin-12 (IL-12), IL-10, and transforming growth factor beta (TGF-beta) mRNA.