Identification of Tumor-Specific Antibodies in Patients With Breast Cancer Vaccinated With Gene-Modified Allogeneic Tumor Cells

Dols, Annemiek; Meijer, Sybren L.; Hu, Hong-Ming; Goodell, Vivian; Disis, Mary L.; Mensdorff‐Pouilly, Silvia von; Verheijen, René H.M.; Alvord, W. Gregory; Smith, John W.; Urba, Walter J.; Fox, Bernard A.

doi:10.1097/00002371-200303000-00009

Cited by 30 publications

(16 citation statements)

References 26 publications

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“…18,[21][22][23]40,41 In addition, some authors have reported differences in the serum protein composition between untreated and heavily pretreated patients, which may influence the differentiation process of DCs. 18,21,23 In accordance with the majority of reports in the literature, 16,39,42,43 similar yield of DCs was obtained in all culture conditions despite the presence or the absence of serum. DCs were characterized for the expression of HLA-DR, CD86, CD83, and CD14.…”

Section: Discussionsupporting

confidence: 88%

A Comparative Analysis of Serum and Serum-free Media for Generation of Clinical Grade DCs

Napoletano

Pinto

Bellati³

et al. 2007

Journal of Immunotherapy

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Dendritic cells (DCs) are the most potent antigen presenting cells and are therefore widely used in cancer immunotherapy. An optimal method for the generation of DCs for clinical use remains to be established. The aim of the study was to find a serum-free media (SFM) able to generate reproducible and functional cultures of DCs for clinical studies. We characterized immature and mature DCs cultured in SFM, CellGro DC and X-VIVO15, and serum media (SM), RPMI 1640+5% human serum or autologous serum. The expression of HLA-DR, CD86, CD83 was higher in SM-cultured DCs (SM-DCs) than SFM-derived DCs (SFM-DCs). Between SFM-DCs, CellGro-cultured DCs (CellGro-DCs) showed a higher expression and an improved up-regulation capacity of all molecules as compared with X-VIVO15-derived DCs (X-VIVO15-DCs). CellGro-DCs and SM-DCs showed a similar mannose receptor expression and related endocytic capacity tested by fluorescein isothiocyanate-dextran uptake. In contrast X-VIVO15-DCs expressed low levels of mannose receptor and were unable to endocyte fluorescein isothiocyanate-dextran. DCs cultured in all conditions stimulated a mix lymphocyte reaction, but CellGro-DCs and SM-DCs induced a more potent T-cell proliferation compared with X-VIVO15-DCs. Cytokine analysis showed that after maturation, all DC cultures produced IL-12p70 and IL-10 except for X-VIVO15-DCs which only produced the latter cytokine. SM-DCs and SFM-DCs induced a TH1 polarization in allogeneic naive T cells. In conclusion, a comparative analysis of DC performance generated in different conditions allows us to determine CellGro DC as the optimal medium for the generation of clinical grade DCs.

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Section: Discussionsupporting

confidence: 88%

A Comparative Analysis of Serum and Serum-free Media for Generation of Clinical Grade DCs

Napoletano

Pinto

Bellati³

et al. 2007

Journal of Immunotherapy

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“…Studies with anti-CTLA-4 monoclonal antibodies, in particular, have sought to identify whether amplification of other T-cell co-stimulatory molecules (35), or antibodies to defined antigenic tumor-associated proteins (33,36), might be useful as biomarkers. For whole cell tumor vaccines where there is not a specific defined antigen being targeted, surrogate antigens known to be expressed by the tumor vaccine have been used as a means of monitoring immune responses from the vaccine (37). The use of immunologically-recognized surrogate antigens, including HER-2/neu, MUC1 and p53, has been possible in the case of breast cancer where IgG responses to these antigens have been identified.…”

Section: Discussionmentioning

confidence: 99%

Antibody responses to prostate‐associated antigens in patients with prostatitis and prostate cancer

Maricque¹,

Eickhoff²,

McNeel³

2010

The Prostate

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BACKGROUNDAn important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum‐based screening approaches have led to the discovery of hundreds of tumor‐associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens; however, prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer.METHODSUsing a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n = 126), patients with chronic prostatitis (n = 45), and men without prostate disease (n = 53).RESULTSWe found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (P < 0.001 and P = 0.003, respectively). Responses to multiple members were not higher in patients with advanced disease, suggesting antibody immune responses occur early in the natural history of cancer progression.CONCLUSIONSThese findings suggest an association between inflammatory conditions of the prostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue. Prostate 71: 134–146, 2011. © 2010 Wiley‐Liss, Inc.

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“…15,22 Five of 7 patients were strongly positive for antibodies to bovine apoB ( Figure 5D and Table 2), perhaps reflecting their extensive exposure in circumstances optimized for immunity. Finally, we examined the sera from HIV-infected patients administered enriched T-cell populations from their HIV-negative twin.…”

Section: Antibodies To Bovine Apob-100 Dominate the Human Immune Respmentioning

confidence: 99%

Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans

Sakamoto

Tsuji

Muul

et al. 2007

Blood

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Recent studies have demonstrated that cell populations intended for therapeutic purposes that are cultured in heterologous animal products can acquire xenoantigens, potentially limiting their utility. In investigations of the immune response to murine embryonic stem cells, we found that a strong antibody response was generated after the second infusion. Both polyclonal and monoclonal antibody responses, derived from immunized mice, were found to be specific for bovine apolipoprotein B-100, which binds to abundant low-density lipoprotein receptors on the cell surface and is internalized. Here we show that in the majority of patients administered 3 different types of cell-based therapies using cells grown in fetal calf serum-containing media, an antibody response to bovine apolipoprotein B-100 develops after the second infusion and is the dominant specificity. The known and potential clinical effects of such antibodies are discussed. (Blood. 2007;110:501-508)

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Identification of Tumor-Specific Antibodies in Patients With Breast Cancer Vaccinated With Gene-Modified Allogeneic Tumor Cells

Cited by 30 publications

References 26 publications

A Comparative Analysis of Serum and Serum-free Media for Generation of Clinical Grade DCs

A Comparative Analysis of Serum and Serum-free Media for Generation of Clinical Grade DCs

Antibody responses to prostate‐associated antigens in patients with prostatitis and prostate cancer

Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans

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