Identification of Peptides for Immunotherapy of Cancer. It is Still Worth the Effort

Mp, Velders; Jd, Nieland; Mp, Rudolf; Loviscek, K; Weijzen, Sanne; Ke, de Visser; Mf, Macedo; Carbone, Michele; Kast, W. Martin

doi:10.1615/critrevimmunol.v18.i1-2.30

Cited by 18 publications

(3 citation statements)

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“…To evaluate the importance of the strong CTL response to TMEV in these animals, we sought to inhibit the development of D b :VP2 121-130 epitope-specific CTL during TMEV infection. Peptides have been used previously to suppress T cell responses in studies involving allergies, tumors, and transplants (16)(17)(18). Administration of the VP2 121-130 peptide 1 day before TMEV infection resulted in the complete inhibition of the immunodominant T cell response against the D b :VP2 121-130 epitope normally observed among brain-infiltrating CD8+ T cells 7 days after infection ( Fig.…”

Section: Inhibition Of the Cd8+ T Cell Response Toward The Immunodomimentioning

confidence: 95%

Preservation of motor function by inhibition of CD8+ virus peptide‐specific T cells in Theiler's virus infection

Johnson¹,

Upshaw²,

Pavelko³

et al. 2001

FASEB j.

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Central nervous system-infiltrating CD8+ T cells are potential mediators of neuropathology in models of multiple sclerosis induced by Theiler's murine encephalomyelitis virus (TMEV) infection. C57BL/6 mice mount a vigorous cytotoxic T lymphocyte (CTL) response against the immunodominant virus peptide VP2121-130 and clear TMEV infection. Interferon-g (IFN-g)R-/- mice also mount a strong CTL response against the VP2121-130 epitope, but because of genetic deficiencies in critical IFN-g signaling pathways, they do not clear TMEV infection and develop prominent neurological deficits within 6 wk. This pronounced disease process, coupled with a defined CTL response, provides an ideal model for evaluating the importance of antiviral CTL activity in the development of severe demyelination and loss of motor neuron function. By administering the VP2121-130 peptide before and during TMEV infection, 99% of the VP2121-130-specific CD8+ T cell response was inhibited. No decrease in virus infection was observed. Peptide treatment did result in significantly less motor dysfunction, even when no differences in levels of demyelination were observed. Although most investigators focus on the role of CD4+ T cells in demyelinating disease, these studies are the first to demonstrate a clear contribution of antiviral CD8+ T cells in neurological injury in a chronic-progressive model of multiple sclerosis.

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Section: Inhibition Of the Cd8+ T Cell Response Toward The Immunodomimentioning

confidence: 95%

Preservation of motor function by inhibition of CD8+ virus peptide‐specific T cells in Theiler's virus infection

Johnson¹,

Upshaw²,

Pavelko³

et al. 2001

FASEB j.

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show abstract

“…The resurgence in cancer vaccine development over the last decade has resulted from identifying tumor-associated peptides and enhancing their presentation to T cells (50,54). Kaech et al (50) noted that effective vaccines must induce as large an effector T cell population as possible, since this burst size determines the number of subsequent memory T cells that form.…”

Section: The Duration Of the Response In Ovatbhsp70-immunized Mice Imentioning

confidence: 99%

The Adjuvant Effects ofMycobacterium tuberculosisHeat Shock Protein 70 Result from the Rapid and Prolonged Activation of Antigen-Specific CD8+ T Cells In Vivo

Harmala

Ingulli

Curtsinger

et al. 2002

The Journal of Immunology

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Heat shock protein 70 (hsp70) is a potent adjuvant that links innate and adaptive immune responses. To study how hsp70 activates naive CD8+ T cells in vivo, we tracked Ag-specific CD8+ T cells in mice immunized with a fusion protein containing chicken OVA linked to hsp70 derived from Mycobacterium tuberculosis (OVA.TBhsp70). On a molar basis, OVA.TBhsp70 was several hundred times more effective than OVA peptide plus CFA in eliciting specific CD8+ T cell responses. Immunization with OVA.TBhsp70 activated >90% of detectable OVA-specific CD8+ T cells within 3 days and led to the persistence of cytotoxic effectors for at least 17 days. These studies demonstrate that the potent adjuvant effect of M. tuberculosis hsp70 results from the relatively complete, rapid, and durable activation of Ag-specific CD8+ T cells.

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“…Because HLA-A2 molecules are frequently expressed in human populations, HLA-A2-restricted melanoma-specific CTL may have significant therapeutic potential for a large number of patients. To optimize their therapeutic value, it is essential to identify the antigenic epitopes that stimulate the CTL response [3].…”

mentioning

confidence: 99%

Identification of Melanoma-specific Peptide Epitopes by HLA-A2.1-restricted Cytotoxic T Lymphocytes

Ge¹,

Wang²,

Wang³

et al. 2006

ABBS

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HLA-A2.1-associated peptides, extracted from human melanoma cells, were used to study epitopes for melanoma-specific HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) by epitope reconstitution, active peptide sequence characterization and synthetic peptide verification. CTL were generated from tumor-involved nodes by in vitro stimulation, initially with autologous melanoma cells and subsequently with allogeneic HLA-A2.1 positive melanoma cells. The CTLs could lyse autologous and allogeneic HLA-A2.1 positive melanomas, but not HLA-A2.1 negative melanomas or HLA-A2.1 positive non-melanomas. The lysis of melanomas could be inhibited by anti-CD3, anti-HLA class I and anti-HLA-A2.1 monoclonal antibodies. HLA-A2.1 molecules were purified from detergent-solubilized human melanoma cells by immunoaffinity column chromatography and further fractionated by reversed phase high performance liquid chromatography. The fractions were assessed for their ability to reconstitute melanoma-specific epitopes with HLA-A2.1 positive antigen-processing mutant T2 cells. Three reconstitution peaks were observed in lactate dehydrogenase release assay. Mass spectrometry and ion-exchange high performance liquid chromatography analysis were used to identify peptide epitopes. Peptides with a mass-to-charge ratio of 948 usually consist of nine amino acid residues. The data from reconstitution experiments confirmed that the synthetic peptides contained epitopes and that the peptides associated with HLA-A2.1 and recognized by melanoma-specific CTL were present in these different melanoma cells. These peptides could be potentially exploited in novel peptide-based antitumor vaccines in immunotherapy for CTL.

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Identification of Peptides for Immunotherapy of Cancer. It is Still Worth the Effort

Cited by 18 publications

References 0 publications

Preservation of motor function by inhibition of CD8+ virus peptide‐specific T cells in Theiler's virus infection

Preservation of motor function by inhibition of CD8+ virus peptide‐specific T cells in Theiler's virus infection

The Adjuvant Effects ofMycobacterium tuberculosisHeat Shock Protein 70 Result from the Rapid and Prolonged Activation of Antigen-Specific CD8+ T Cells In Vivo

Identification of Melanoma-specific Peptide Epitopes by HLA-A2.1-restricted Cytotoxic T Lymphocytes

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