Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2

Koichi Yamazaki, Gina Spruill, Joseph Rhoderick, Julie Spielman, Niramol Savaraj, Eckhard R. Podack

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Tumor-derived peptides presented by MHC class I molecules are targets for tumor rejection by CD8+ CTLs. MHC-restricted CD8+ CTLs are required also for the identification and characterization of tumor antigens that will be useful for immune therapy. For many human solid tumors, however, tumor antigens remain undefined because of the difficulty of generating MHC- restricted, tumor-specific CTLs required for their analysis. CD8+ CTL responses are modulated by CD4+ helper T cells and by antigen-Presenting cells. In this study, highly purified cD8+ T cells were mixed with tumor cells in primary cultures in the absence of any other cells to reduce the complexity of CTL generation. Tumor cells were transfected with HLA-A1 or HLA-A2 and used to stimulate partly matched HLA-A1- or HLA-A2-positive CD8+ T cells. Partial MHC class I matching of tumor and CD8+ T cells and omission of other cells in primary culture was highly effective in generating MHC class I-restricted CTL to poorly immunogenic small cell lung carcinomas (SCLCs). Cytotoxicity was further enhanced by cotransfection of tumor cells with B7.1 (CD80). ICAM-1 (CD54) was not as effective as costimulation. SCLC cells presented tumor-specific peptides with HLA-A1 and HLA-A2 and were lysed by A1- or A2-restricted CD8+ CTLs. A1- and A2-restricted CD8+ CTLs detected shared tumor antigens on unrelated SCLC tumor lines in addition to private antigens. The use of direct antigen presentation by MHC class I-transfected tumors to MHC class I-matched CD8+ T cells is an effective way to generate MHC class I-restricted CTLs toward poorly immunogenic tumors in vitro, permitting the molecular identification of their tumor antigens.

Original languageEnglish
Pages (from-to)4642-4650
Number of pages9
JournalCancer Research
Volume59
Issue number18
StatePublished - Sep 15 1999

Fingerprint

HLA-A1 Antigen
HLA-A2 Antigen
Small Cell Lung Carcinoma
Neoplasm Antigens
Neoplasms
T-Lymphocytes
Primary Cell Culture
varespladib methyl
Peptides
Viral Tumor Antigens
Antigen Presentation
Antigen-Presenting Cells
Intercellular Adhesion Molecule-1
Helper-Inducer T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yamazaki, K., Spruill, G., Rhoderick, J., Spielman, J., Savaraj, N., & Podack, E. R. (1999). Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2. Cancer Research, 59(18), 4642-4650.

Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2. / Yamazaki, Koichi; Spruill, Gina; Rhoderick, Joseph; Spielman, Julie; Savaraj, Niramol; Podack, Eckhard R.

In: Cancer Research, Vol. 59, No. 18, 15.09.1999, p. 4642-4650.

Research output: Contribution to journalArticle

Yamazaki, K, Spruill, G, Rhoderick, J, Spielman, J, Savaraj, N & Podack, ER 1999, 'Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2', Cancer Research, vol. 59, no. 18, pp. 4642-4650.
Yamazaki K, Spruill G, Rhoderick J, Spielman J, Savaraj N, Podack ER. Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2. Cancer Research. 1999 Sep 15;59(18):4642-4650.
Yamazaki, Koichi ; Spruill, Gina ; Rhoderick, Joseph ; Spielman, Julie ; Savaraj, Niramol ; Podack, Eckhard R. / Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2. In: Cancer Research. 1999 ; Vol. 59, No. 18. pp. 4642-4650.
@article{a008e57b371f4ea9a69f954af2661d60,
title = "Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2",
abstract = "Tumor-derived peptides presented by MHC class I molecules are targets for tumor rejection by CD8+ CTLs. MHC-restricted CD8+ CTLs are required also for the identification and characterization of tumor antigens that will be useful for immune therapy. For many human solid tumors, however, tumor antigens remain undefined because of the difficulty of generating MHC- restricted, tumor-specific CTLs required for their analysis. CD8+ CTL responses are modulated by CD4+ helper T cells and by antigen-Presenting cells. In this study, highly purified cD8+ T cells were mixed with tumor cells in primary cultures in the absence of any other cells to reduce the complexity of CTL generation. Tumor cells were transfected with HLA-A1 or HLA-A2 and used to stimulate partly matched HLA-A1- or HLA-A2-positive CD8+ T cells. Partial MHC class I matching of tumor and CD8+ T cells and omission of other cells in primary culture was highly effective in generating MHC class I-restricted CTL to poorly immunogenic small cell lung carcinomas (SCLCs). Cytotoxicity was further enhanced by cotransfection of tumor cells with B7.1 (CD80). ICAM-1 (CD54) was not as effective as costimulation. SCLC cells presented tumor-specific peptides with HLA-A1 and HLA-A2 and were lysed by A1- or A2-restricted CD8+ CTLs. A1- and A2-restricted CD8+ CTLs detected shared tumor antigens on unrelated SCLC tumor lines in addition to private antigens. The use of direct antigen presentation by MHC class I-transfected tumors to MHC class I-matched CD8+ T cells is an effective way to generate MHC class I-restricted CTLs toward poorly immunogenic tumors in vitro, permitting the molecular identification of their tumor antigens.",
author = "Koichi Yamazaki and Gina Spruill and Joseph Rhoderick and Julie Spielman and Niramol Savaraj and Podack, {Eckhard R.}",
year = "1999",
month = "9",
day = "15",
language = "English",
volume = "59",
pages = "4642--4650",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "18",

}

TY - JOUR

T1 - Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2

AU - Yamazaki, Koichi

AU - Spruill, Gina

AU - Rhoderick, Joseph

AU - Spielman, Julie

AU - Savaraj, Niramol

AU - Podack, Eckhard R.

PY - 1999/9/15

Y1 - 1999/9/15

N2 - Tumor-derived peptides presented by MHC class I molecules are targets for tumor rejection by CD8+ CTLs. MHC-restricted CD8+ CTLs are required also for the identification and characterization of tumor antigens that will be useful for immune therapy. For many human solid tumors, however, tumor antigens remain undefined because of the difficulty of generating MHC- restricted, tumor-specific CTLs required for their analysis. CD8+ CTL responses are modulated by CD4+ helper T cells and by antigen-Presenting cells. In this study, highly purified cD8+ T cells were mixed with tumor cells in primary cultures in the absence of any other cells to reduce the complexity of CTL generation. Tumor cells were transfected with HLA-A1 or HLA-A2 and used to stimulate partly matched HLA-A1- or HLA-A2-positive CD8+ T cells. Partial MHC class I matching of tumor and CD8+ T cells and omission of other cells in primary culture was highly effective in generating MHC class I-restricted CTL to poorly immunogenic small cell lung carcinomas (SCLCs). Cytotoxicity was further enhanced by cotransfection of tumor cells with B7.1 (CD80). ICAM-1 (CD54) was not as effective as costimulation. SCLC cells presented tumor-specific peptides with HLA-A1 and HLA-A2 and were lysed by A1- or A2-restricted CD8+ CTLs. A1- and A2-restricted CD8+ CTLs detected shared tumor antigens on unrelated SCLC tumor lines in addition to private antigens. The use of direct antigen presentation by MHC class I-transfected tumors to MHC class I-matched CD8+ T cells is an effective way to generate MHC class I-restricted CTLs toward poorly immunogenic tumors in vitro, permitting the molecular identification of their tumor antigens.

AB - Tumor-derived peptides presented by MHC class I molecules are targets for tumor rejection by CD8+ CTLs. MHC-restricted CD8+ CTLs are required also for the identification and characterization of tumor antigens that will be useful for immune therapy. For many human solid tumors, however, tumor antigens remain undefined because of the difficulty of generating MHC- restricted, tumor-specific CTLs required for their analysis. CD8+ CTL responses are modulated by CD4+ helper T cells and by antigen-Presenting cells. In this study, highly purified cD8+ T cells were mixed with tumor cells in primary cultures in the absence of any other cells to reduce the complexity of CTL generation. Tumor cells were transfected with HLA-A1 or HLA-A2 and used to stimulate partly matched HLA-A1- or HLA-A2-positive CD8+ T cells. Partial MHC class I matching of tumor and CD8+ T cells and omission of other cells in primary culture was highly effective in generating MHC class I-restricted CTL to poorly immunogenic small cell lung carcinomas (SCLCs). Cytotoxicity was further enhanced by cotransfection of tumor cells with B7.1 (CD80). ICAM-1 (CD54) was not as effective as costimulation. SCLC cells presented tumor-specific peptides with HLA-A1 and HLA-A2 and were lysed by A1- or A2-restricted CD8+ CTLs. A1- and A2-restricted CD8+ CTLs detected shared tumor antigens on unrelated SCLC tumor lines in addition to private antigens. The use of direct antigen presentation by MHC class I-transfected tumors to MHC class I-matched CD8+ T cells is an effective way to generate MHC class I-restricted CTLs toward poorly immunogenic tumors in vitro, permitting the molecular identification of their tumor antigens.

UR - http://www.scopus.com/inward/record.url?scp=0033568150&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033568150&partnerID=8YFLogxK

M3 - Article

VL - 59

SP - 4642

EP - 4650

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 18

ER -