Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes Journal Article

   


Authors: Krause, A.; Guo, H. F.; Latouche, J. B.; Tan, C.; Cheung, N. K. V.; Sadelain, M.
Article Title: Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes
Abstract: Most tumor cells function poorly as antigen-presenting cells in part because they do not express costimulatory molecules. To provide costimulation to T lymphocytes that recognize tumor cells, we constructed a CD28-like receptor specific for G(D2), a ganglioside overexpressed on the surface of neuroblastoma, small-cell lung carcinoma, melanoma, and other human tumors. Recognition of G(D2) was provided by a single-chain antibody derived from the G(D2)-specific monoclonal antibody 3G6. We demonstrate that the chimeric receptor 3G6-CD28 provides CD28 signaling upon specific recognition of the G(D2) antigen on tumor cells. Human primary T lymphocytes retrovirally transduced with 3G6-CD28 secrete interleukin 2, survive proapoptotic culture conditions, and selectively undergo clonal expansion in the presence of an antiidiotypic antibody specific for 3G6-CD28. Polyclonal CD8+ lymphocytes expressing 3G6-CD28 are selectively expanded when cultured with cells expressing allogeneic major histocompatibility complex class I together with G(D2). Primary T cells given such an antigen-dependent survival advantage should be very useful to augment immune responses against tumor cells.
Keywords: signal transduction; survival; human cell; nonhuman; cd8 antigen; lymphocyte proliferation; t lymphocyte; antigens, cd3; t-lymphocytes; animal cell; mouse; animals; mice; cell survival; cells, cultured; cell division; interleukin 2; reverse transcription polymerase chain reaction; apoptosis; enzyme linked immunosorbent assay; gene transfer; monoclonal antibody; rna; t lymphocyte receptor; lymphocyte activation; immune response; recombinant fusion proteins; ganglioside gd2; antigen recognition; peptides; adoptive cell therapy; receptor; histocompatibility antigens class ii; antibody; antigen presenting cell; cd28 antigen; antigens, cd28; interleukin-2; major histocompatibility antigen class 1; coculture; gangliosides; costimulation; ganglioside; interleukin 2 receptor; receptors, interleukin-2; antibodies, anti-idiotypic; chimeric receptors; antiidiotypic antibody; humans; human; priority journal; article
Journal Title: Journal of Experimental Medicine
Volume: 188
Issue: 4
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 1998-08-17
Start Page: 619
End Page: 626
Language: English
DOI: 10.1084/jem.188.4.619
PUBMED: 9705944
PROVIDER: scopus
PMCID: PMC2213361
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032541385&doi=10.1084%2fjem.188.4.619&partnerID=40&md5=85361ac2f57455c15a1dcaaedbfa1275
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
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MSK Authors
  1. Nai-Kong Cheung
    648 Cheung
  2. Jean-Baptiste P Latouche
    23 Latouche
  3. Michel W J Sadelain
    583 Sadelain
  4. Hong-Fen Guo
    73 Guo
  5. Cuiwen Tan
    11 Tan
  6. Anja Krause
    6 Krause
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