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Overexpressed oncogenic tumor-self antigens

New vaccine targets

, &
Pages 3297-3305 | Received 02 May 2014, Accepted 04 Jun 2014, Published online: 01 Nov 2014

Figures & data

Figure 1. Immunologic character of tumor antigens. Simplified tumor antigen classification based on the immunologic character of the tumor antigen relative to its potential immunogenicity. Depicted are two main classes of antigens represented by tumor-specific and -associated antigens defined by normal cell expression, and four sub-classes ranging from stronger to weaker immunity. Non-self (e.g., viral proteins) and altered-self (e.g., mutant protein or restricted expression) antigens are proposed to elicit strong immune responses, and self antigens, whether involved in oncogenesis (tumor-dependent) or not (tumor-independent), would elicit weaker immune responses.

Figure 1. Immunologic character of tumor antigens. Simplified tumor antigen classification based on the immunologic character of the tumor antigen relative to its potential immunogenicity. Depicted are two main classes of antigens represented by tumor-specific and -associated antigens defined by normal cell expression, and four sub-classes ranging from stronger to weaker immunity. Non-self (e.g., viral proteins) and altered-self (e.g., mutant protein or restricted expression) antigens are proposed to elicit strong immune responses, and self antigens, whether involved in oncogenesis (tumor-dependent) or not (tumor-independent), would elicit weaker immune responses.

Table 1. TPD52 vaccines in murine models of sarcoma and prostate cancer

Figure 2. Generation of CTLs from normal PBLs with D52 peptide. The data show hD52-specific HLA-A2-restricted killing of human prostate cell lines. hD52 expression in the human prostate cell lines was determined by 30 cycle RT-PCR using hD52-specific primers and GAPDH as an internal reference. (A) Human normal prostate cell line 568 NPTX and tumor cell line LnCap are hD52-low expressors. (B) Killing of human prostate cancer cell lines determined using a standard lysis assay at an E:T of 5:1. Targets: human prostate cancer and normal-derived cells from HLA-A2+ patient 568 (normal = NPTX, tumor = CP1TX and CP2TX) were generated as previously described,Citation103 human prostate cancer cell lines PC-3 (HLA-A2-) and LnCap (HLA-A2+) are commercially available. Methods: The method used to generate hD52 peptide-specific CTLs by IVS with hD52 peptide Q(A/L)FSHSFS(I/V) has been previously explained in detail.Citation102

Figure 2. Generation of CTLs from normal PBLs with D52 peptide. The data show hD52-specific HLA-A2-restricted killing of human prostate cell lines. hD52 expression in the human prostate cell lines was determined by 30 cycle RT-PCR using hD52-specific primers and GAPDH as an internal reference. (A) Human normal prostate cell line 568 NPTX and tumor cell line LnCap are hD52-low expressors. (B) Killing of human prostate cancer cell lines determined using a standard lysis assay at an E:T of 5:1. Targets: human prostate cancer and normal-derived cells from HLA-A2+ patient 568 (normal = NPTX, tumor = CP1TX and CP2TX) were generated as previously described,Citation103 human prostate cancer cell lines PC-3 (HLA-A2-) and LnCap (HLA-A2+) are commercially available. Methods: The method used to generate hD52 peptide-specific CTLs by IVS with hD52 peptide Q(A/L)FSHSFS(I/V) has been previously explained in detail.Citation102