Recognition of human colon cancer by T cells transduced with a chimeric receptor gene

被引:45
作者
Daly, T
Royal, RE
Kershaw, MH
Treisman, J
Wang, G
Li, WP
Herlyn, D
Eshhar, Z
Hwu, P
机构
[1] NCI, NIH, Surg Branch, Tumor Immunol Sect, Bethesda, MD 20892 USA
[2] Univ Penn, Sch Med, Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA
[3] Weizmann Inst Sci, IL-76100 Rehovot, Israel
基金
英国医学研究理事会;
关键词
immunotherapy; colon cancer; lymphocyte; gene therapy; redirection;
D O I
10.1038/sj.cgt.7700121
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Transduction with chimeric T-cell receptor genes can be used to redirect primary T lymphocytes to recognize specific antigens (Ags), including, ovarian and breast cancer Ags. To extend this approach to colon cancer we report here redirection of T cells using a chimeric receptor recognizing the colon cancer-associated Ag EGP40. Chimeric T cell receptors were constructed by ligating single-chain genes of either of two EGP40-specific monoclonal antibodies (CO17.1A, GA733) to the Fe receptor gamma-signaling chain. Retroviral vectors incorporating these constructs were used to transduce a murine T-cell line and human peripheral blood lymphocytes. These modified T cells were analyzed for specific recognition of colon cancer lines by measuring cytokine release and lyric activity against tumor targets. Murine lymphocytes transduced with the chimeric receptor based on GA733, but not CO17.1A, released cytokine specifically in response to EGP40-expressing colon cancer cell lines. Recognition of colon cancer targets by murine lymphocytes was blocked by the addition of GA733 antibody or soluble EGP40 Ag, confirming that colon cancer recognition is based on specific chimeric receptor-Ag interaction. Human lymphocytes transduced with chimeric GA733 specifically recognized colon carcinoma cells in cytokine release assays and lysed EGP40-expressing tumor cells. Genetic modification of T cells can be used to redirect T cells against EGP40-expressing tumor cells. The expression of chimeric GA733 in the autologous lymphocytes of patients may provide a source of tumor-reactive cells with therapeutic application against colon cancer.
引用
收藏
页码:284 / 291
页数:8
相关论文
共 50 条
  • [1] *ADV COL CANC MET, 1992, J CLIN ONCOL, V10, P869
  • [2] BALLANTYNE GH, 1993, CANCER, V71, P4252, DOI 10.1002/1097-0142(19930615)71:12+<4252::AID-CNCR2820711815>3.0.CO
  • [3] 2-6
  • [4] Colorectal carcinoma invasion inhibition by CO17-1A/GA733 antigen and its murine homologue
    Basak, S
    Speicher, D
    Eck, S
    Wunner, W
    Maul, G
    Simmons, MS
    Herlyn, D
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (09): : 691 - 697
  • [5] BERKOWER I, 1985, J IMMUNOL, V135, P2628
  • [6] CAMBIER JC, 1995, J IMMUNOL, V155, P3281
  • [7] HUMAN ANTIIDIOTYPIC ANTIBODIES INDUCED A HUMORAL AND CELLULAR IMMUNE-RESPONSE AGAINST A COLORECTAL CARCINOMA-ASSOCIATED ANTIGEN IN PATIENTS
    FAGERBERG, J
    STEINITZ, M
    WIGZELL, H
    ASKELOF, P
    MELLSTEDT, H
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (11) : 4773 - 4777
  • [8] GOTTLINGER HG, 1986, INT J CANCER, V38, P47
  • [9] EXPRESSION OF IMMUNOGLOBULIN-T-CELL RECEPTOR CHIMERIC MOLECULES AS FUNCTIONAL RECEPTORS WITH ANTIBODY-TYPE SPECIFICITY
    GROSS, G
    WAKS, T
    ESHHAR, Z
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (24) : 10024 - 10028
  • [10] Hekele A, 1996, INT J CANCER, V68, P232, DOI 10.1002/(SICI)1097-0215(19961009)68:2<232::AID-IJC16>3.0.CO