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Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes.

Andersen ML, Ruhwald M, Thorn M, Pedersen AE, Mathiassen S, Buus S, Claesson MH - J Immune Based Ther Vaccines (2003)

Bottom Line: Six of the peptides generated specific CTL responses after immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth.However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance.Our data would indicate that vaccination with immunogenic peptides derived from potentially overexpressed tumor proteins, as identified by mRNA expression profiling of p53-/- thymoma cells, at best results in a weak tumor protection thus questioning this way of detection of new tumor rejection epitopes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Anatomy, University of Copenhagen, Copenhagen, Denmark. M.H.Claesson@mai.ku.dk

ABSTRACT
Thirteen H-2b-binding peptides derived from six potentially overexpressed proteins in p53-/- thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take, suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides derived from potentially overexpressed tumor proteins, as identified by mRNA expression profiling of p53-/- thymoma cells, at best results in a weak tumor protection thus questioning this way of detection of new tumor rejection epitopes.

No MeSH data available.


Related in: MedlinePlus

Survival of naïve and RAD23–31/ RAD24–31 vaccinated mice inoculated subcutaneously with 106 SM7 tumor cells. The curves represent the pooled data from two separate experiments with 15 mice per group. The curves are significantly different, p < 0.03. The mean survival time for controls and vaccinated mice was 44 and 55 days respectively.
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Figure 3: Survival of naïve and RAD23–31/ RAD24–31 vaccinated mice inoculated subcutaneously with 106 SM7 tumor cells. The curves represent the pooled data from two separate experiments with 15 mice per group. The curves are significantly different, p < 0.03. The mean survival time for controls and vaccinated mice was 44 and 55 days respectively.

Mentions: Groups of 7–8 mice were vaccinationated three times with a pool of the six RAD50 peptides or a mixture of the two immunogenic RAD23–31 and RAD24–31 peptides. The RAD50 peptides were mixed with equal amounts of FIA and a helper peptide, TPPAYRPPNAPIL [14] was included. Control mice received FIA and helper peptide only. Fig. 3 shows the pooled survival curves for two separate experiments. A significant protection against tumor take was obtained in mice vaccinated with a mixture of RAD23–31 and RAD24–31 peptides (p < 0.03). In disagreement with our previous study [8], vaccination with a mixture of the six RAD50 peptides did not offer any protection in these experiments (data not shown). Two of five vaccine protected mice in Fig. 3 were rechallenge with 106 tumor cells 3 months after the primary tumor challenge. Two of the mice developed progressing tumors, suggesting low immunological memory for tumor rejection antigens (data not included). Fig. 4 shows data from one of two experiments with mice immunized with a mixture of the 4 immunogenic peptides depicted in Fig. 2. These peptides are derived from four potentially upregulated SM-7 proteins not related to the RAD50 protein (Table 1). No evidence of protection was obtained after immunization with this serie of peptides in the two separate, but identical vaccination series.


Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes.

Andersen ML, Ruhwald M, Thorn M, Pedersen AE, Mathiassen S, Buus S, Claesson MH - J Immune Based Ther Vaccines (2003)

Survival of naïve and RAD23–31/ RAD24–31 vaccinated mice inoculated subcutaneously with 106 SM7 tumor cells. The curves represent the pooled data from two separate experiments with 15 mice per group. The curves are significantly different, p < 0.03. The mean survival time for controls and vaccinated mice was 44 and 55 days respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC153425&req=5

Figure 3: Survival of naïve and RAD23–31/ RAD24–31 vaccinated mice inoculated subcutaneously with 106 SM7 tumor cells. The curves represent the pooled data from two separate experiments with 15 mice per group. The curves are significantly different, p < 0.03. The mean survival time for controls and vaccinated mice was 44 and 55 days respectively.
Mentions: Groups of 7–8 mice were vaccinationated three times with a pool of the six RAD50 peptides or a mixture of the two immunogenic RAD23–31 and RAD24–31 peptides. The RAD50 peptides were mixed with equal amounts of FIA and a helper peptide, TPPAYRPPNAPIL [14] was included. Control mice received FIA and helper peptide only. Fig. 3 shows the pooled survival curves for two separate experiments. A significant protection against tumor take was obtained in mice vaccinated with a mixture of RAD23–31 and RAD24–31 peptides (p < 0.03). In disagreement with our previous study [8], vaccination with a mixture of the six RAD50 peptides did not offer any protection in these experiments (data not shown). Two of five vaccine protected mice in Fig. 3 were rechallenge with 106 tumor cells 3 months after the primary tumor challenge. Two of the mice developed progressing tumors, suggesting low immunological memory for tumor rejection antigens (data not included). Fig. 4 shows data from one of two experiments with mice immunized with a mixture of the 4 immunogenic peptides depicted in Fig. 2. These peptides are derived from four potentially upregulated SM-7 proteins not related to the RAD50 protein (Table 1). No evidence of protection was obtained after immunization with this serie of peptides in the two separate, but identical vaccination series.

Bottom Line: Six of the peptides generated specific CTL responses after immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth.However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance.Our data would indicate that vaccination with immunogenic peptides derived from potentially overexpressed tumor proteins, as identified by mRNA expression profiling of p53-/- thymoma cells, at best results in a weak tumor protection thus questioning this way of detection of new tumor rejection epitopes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Anatomy, University of Copenhagen, Copenhagen, Denmark. M.H.Claesson@mai.ku.dk

ABSTRACT
Thirteen H-2b-binding peptides derived from six potentially overexpressed proteins in p53-/- thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take, suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides derived from potentially overexpressed tumor proteins, as identified by mRNA expression profiling of p53-/- thymoma cells, at best results in a weak tumor protection thus questioning this way of detection of new tumor rejection epitopes.

No MeSH data available.


Related in: MedlinePlus