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Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity.

Publication ,  Journal Article
Sittler, T; Zhou, J; Park, J; Yuen, NK; Sarantopoulos, S; Mollick, J; Salgia, R; Giobbie-Hurder, A; Dranoff, G; Hodi, FS
Published in: Clin Cancer Res
June 15, 2008

PURPOSE: The therapeutic importance of immune responses against single versus multiple antigens is poorly understood. There also remains insufficient understanding whether responses to one subset of antigens are more significant than another. Autoantibodies are frequent in cancer patients. They can pose no biological significance or lead to debilitating paraneoplastic syndromes. Autoreactivity has been associated with clinical benefits, but the magnitude necessary for meaningful results is unknown. Autologous tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor generate immune infiltrates in preexisting metastases with associated tumor destruction. We sought to identify targets of responses from this vaccination strategy. EXPERIMENTAL DESIGN: Postvaccination sera used in screening a cDNA expression library prepared from a densely infiltrated metastasis of a long-term surviving melanoma patient identified several autoantigens. Additional autoantigens were identified through similar screenings in non-small cell lung cancer and murine models, and proteins implicated in cancer propagation. ELISAs for several targets were established using recombinant proteins, whereas others were evaluated by petit serologies. RESULTS: Eleven gene products were identified through serologic screening from two patients showing highly favorable clinical outcomes. A subset of antigens revealed significant changes in antibody titers compared with weak responses to other proteins. Time course analyses showed coordinated enhanced titers against several targets as a function of vaccination in responding patients. CONCLUSIONS: This study shows the range of biologically significant antigens resulting from a whole-cell vaccine. Targets include autoantigens that are components of cell cycle regulation. Potent antibody responses against multiple autoantigens are associated with effective tumor destruction without clinical autoimmunity.

Duke Scholars

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

June 15, 2008

Volume

14

Issue

12

Start / End Page

3896 / 3905

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Treatment Outcome
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasms
  • Lymphocytes, Tumor-Infiltrating
  • Immunotherapy
  • Humans
  • Cell Line, Tumor
  • Cancer Vaccines
 

Citation

APA
Chicago
ICMJE
MLA
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Sittler, T., Zhou, J., Park, J., Yuen, N. K., Sarantopoulos, S., Mollick, J., … Hodi, F. S. (2008). Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity. Clin Cancer Res, 14(12), 3896–3905. https://doi.org/10.1158/1078-0432.CCR-07-4782
Sittler, Taylor, Jun Zhou, Joosang Park, Noah K. Yuen, Stefanie Sarantopoulos, Joseph Mollick, Ravi Salgia, Anita Giobbie-Hurder, Glenn Dranoff, and F Stephen Hodi. “Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity.Clin Cancer Res 14, no. 12 (June 15, 2008): 3896–3905. https://doi.org/10.1158/1078-0432.CCR-07-4782.
Sittler T, Zhou J, Park J, Yuen NK, Sarantopoulos S, Mollick J, et al. Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity. Clin Cancer Res. 2008 Jun 15;14(12):3896–905.
Sittler, Taylor, et al. “Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity.Clin Cancer Res, vol. 14, no. 12, June 2008, pp. 3896–905. Pubmed, doi:10.1158/1078-0432.CCR-07-4782.
Sittler T, Zhou J, Park J, Yuen NK, Sarantopoulos S, Mollick J, Salgia R, Giobbie-Hurder A, Dranoff G, Hodi FS. Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity. Clin Cancer Res. 2008 Jun 15;14(12):3896–3905.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

June 15, 2008

Volume

14

Issue

12

Start / End Page

3896 / 3905

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Treatment Outcome
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasms
  • Lymphocytes, Tumor-Infiltrating
  • Immunotherapy
  • Humans
  • Cell Line, Tumor
  • Cancer Vaccines