Foreign antigenic peptides delivered to the tumor as targets of cytotoxic T cells

Wei, Wei Zen; Ratner, Stuart; Shibuya, Terry Y.; Yoo, George H.; Jáni, Ágnes

doi:10.1016/s0022-1759(01)00484-7

Cited by 20 publications

(16 citation statements)

References 21 publications

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“…1). It is important to note that BALB/c mice respond very strongly to the T cell epitope of A␤ 42 (32) and only moderately to the PADRE T cell epitope (39). Thus, even though BALB/c mice are low responders to PADRE, they still generated a strong anti-A␤ 42 response.…”

Section: Discussionmentioning

confidence: 98%

“…For our epitope vaccine we chose a universal synthetic, nonnatural pan HLA DR-binding epitope, PADRE, which was engineered to provide a Th cell epitope that is chemically defined, easily manufactured, and able to generate effective Th cell responses in the general human population. PADRE binds with high affinity to 15 of 16 of the most common HLA-DR types tested to date (37)(38)(39)(40)(41)(42)(43). When PADRE was tested against human T cells in a proliferation assay, it was found to be 100-fold more potent on a molar basis than a tetanus-derived universal epitope.…”

Section: Discussionmentioning

confidence: 99%

“…When PADRE was tested against human T cells in a proliferation assay, it was found to be 100-fold more potent on a molar basis than a tetanus-derived universal epitope. PADRE also binds with high to intermediate affinity to mouse I-A b/d and I-E b/d MHC haplotypes (37,39,41,42). In addition, PADRE has been shown to be safe and well tolerated in human clinical trials (40).…”

Section: Discussionmentioning

confidence: 99%

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Prototype Alzheimer’s Disease Vaccine Using the Immunodominant B Cell Epitope from β-Amyloid and Promiscuous T Cell Epitope Pan HLA DR-Binding Peptide

Agadjanyan

Ghochikyan

Petrushina³

et al. 2005

The Journal of Immunology

180

177

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Immunization of amyloid precursor protein transgenic mice with fibrillar β-amyloid (Aβ) prevents Alzheimer’s disease (AD)-like neuropathology. The first immunotherapy clinical trial used fibrillar Aβ, containing the B and T cell self epitopes of Aβ, as the immunogen formulated with QS21 as the adjuvant in the vaccine. Unfortunately, the clinical trial was halted during the phase II stage when 6% of the participants developed meningoencephalitis. The cause of the meningoencephalitis in the patients that received the vaccine has not been definitively determined; however, analysis of two case reports from the AN-1792 vaccine trial suggest that the meningoencephalitis may have been caused by a T cell-mediated autoimmune response, whereas production of anti-Aβ Abs may have been therapeutic to the AD patients. Therefore, to reduce the risk of an adverse T cell-mediated immune response to Aβ immunotherapy we have designed a prototype epitope vaccine that contains the immunodominant B cell epitope of Aβ in tandem with the synthetic universal Th cell pan HLA DR epitope, pan HLA DR-binding peptide (PADRE). Importantly, the PADRE-Aβ1–15 sequence lacks the T cell epitope of Aβ. Immunization of BALB/c mice with the PADRE-Aβ1–15 epitope vaccine produced high titers of anti-Aβ Abs. Splenocytes from immunized mice showed robust T cell stimulation in response to peptides containing PADRE. However, splenocytes from immunized mice were not reactivated by the Aβ peptide. New preclinical trials in amyloid precursor protein transgenic mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse events that occurred in the first clinical trial.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prototype Alzheimer’s Disease Vaccine Using the Immunodominant B Cell Epitope from β-Amyloid and Promiscuous T Cell Epitope Pan HLA DR-Binding Peptide

Agadjanyan

Ghochikyan

Petrushina³

et al. 2005

The Journal of Immunology

180

177

View full text Add to dashboard Cite

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“…PA-DRE may also be involved in the rejection of tumors when associated with a CD8-reactive foreign peptide (34). An interesting problem is the contrast between the selective induction of a mucosal response and the low level of serum Abs.…”

Section: Discussionmentioning

confidence: 99%

Impairment by Mucosal Adjuvants and Cross-Reactivity with Variant Peptides of the Mucosal Immunity Induced by Injection of the Fusion Peptide PADRE-ELDKWA

Decroix

Pamonsinlapatham

Quan

et al. 2003

Clin Vaccine Immunol

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Secretory immunity protects against mucosal transmission of viruses, as demonstrated with the oral poliovirus vaccine. In a previous study we showed that this immunity could be induced in mice by injection of a fusion peptide consisting of an unnatural peptide-like sequence (PADRE) and a viral epitope (ELDKWASLW). PADRE is a T-helper-cell epitope able to bind most major histocompatibility complex class II molecules of different haplotypes in mice and humans and to increase antibody responses. ELDKWA is a well-known consensual sequence of gp41 involved in a key structure of human immunodeficiency virus (HIV) type 1. Here, the antibody response to the native form of ELDKWA was mainly of the immunoglobulin A isotype and selectively occurred in mucosa. Adjuvants, such as cholera toxin and cytosine polyguanine, were useless and even competed with PADRE for the response. Interestingly, these antibodies were cross-reactive with the three major variants of the epitope, as shown both by direct enzyme-linked immunosorbent assay and by inhibition. This unconventional route of mucosal immunization allows control of the administered dose. The lack of adjuvant and the cross-reactivity of the antibodies increase the safety and the spectrum of the candidate vaccine, respectively. The drug-like nature of the construct suggests further improvements by synthesis of more antigenic sequences. The reasonable cost of short peptides at the industrial level and their purity make this approach of interest for future vaccines against mucosal transmission of HIV or other pathogens.

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“…PADRE has been used previously with additional adjuvants, resulting in enhanced Ab titer, CTL activity, IFN-g secretion, lymphocyte proliferation, or tumor immunity (40)(41)(42)(43)(44). Only the combination of PADRE and CpG or cholera toxin in an HIV peptide-based vaccine reduced the IgA response (45).…”

Section: Discussionmentioning

confidence: 99%

Induction of Homologous Rather than Heterologous Antigen-Specific CD4 T Cell Responses Is Critical for Functional CD8 T Cell Responses in Mice Transgenic for a Foreign Antigen

Sabarth

Chamberlain

Brett

et al. 2010

The Journal of Immunology

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Foreign antigenic peptides delivered to the tumor as targets of cytotoxic T cells

Cited by 20 publications

References 21 publications

Prototype Alzheimer’s Disease Vaccine Using the Immunodominant B Cell Epitope from β-Amyloid and Promiscuous T Cell Epitope Pan HLA DR-Binding Peptide

Prototype Alzheimer’s Disease Vaccine Using the Immunodominant B Cell Epitope from β-Amyloid and Promiscuous T Cell Epitope Pan HLA DR-Binding Peptide

Impairment by Mucosal Adjuvants and Cross-Reactivity with Variant Peptides of the Mucosal Immunity Induced by Injection of the Fusion Peptide PADRE-ELDKWA

Induction of Homologous Rather than Heterologous Antigen-Specific CD4 T Cell Responses Is Critical for Functional CD8 T Cell Responses in Mice Transgenic for a Foreign Antigen

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