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ABSTRACT Antitumor immune responses are mediated primarily by T cells1. Downregulation of the major histocompatiblity complex (MHC) and the molecules that costimulate the immune response is

associated with defective signaling by tumor cells for T-cell activation2–14. _In vitro_ treatment with a combination of cytokines significantly increased the expression of MHC class I and

adhesion molecules on tumor cell surfaces. When tumor cells were first incubated with a bispecific monoclonal antibody that binds antigen on tumor cells to CD28 on T cells, the modified

tumor cells become immunogenic and are able to stimulate naive T cells, generating tumor-specific cytotoxic T cells _in vitro_. Immunization with the modified tumor cells elicits an immune

response mediated by CD8+ T cells. This response protected against a challenge with parental tumor cells and cured established tumors. The approach was effective in both low immunogenic and

nonimmunogenic tumor model systems. Modification of tumor cells with this two-step procedure may provide a strategy for development of tumor vaccines that is effective for cancer

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references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Tumor Immunology & Gene Therapy Center, Institute of Hepatobiliary Surgery and Changhai Hospital, the Shanghai Second Military

Medical University, Shanghai, 200433, People's Republic of China Ya-Jun Guo, Xiao-Yan Che, Feng Shen, Tian-Pei Xie, Jing Ma, Xiao-Ning Wang, Shu-Guang Wu & Meng-Chao Wu * Department

of Pathology, Cancer Research Center, Case Western Reserve University School of Medicine and the University Hospitals of Cleveland, Cleveland, Ohio, 44106, USA Ya-Jun Guo & Jing Ma *

Department of Pharmacology, Cancer Research Center, Case Western Reserve University School of Medicine and the University Hospitals of Cleveland, Cleveland, Ohio, 44106, USA Donald D.

Anthony * Tumor Vaccine Program, Sidney Kimmel Cancer Center, San Diego, California, 92121, USA Ya-Jun Guo Authors * Ya-Jun Guo View author publications You can also search for this author

inPubMed Google Scholar * Xiao-Yan Che View author publications You can also search for this author inPubMed Google Scholar * Feng Shen View author publications You can also search for this

author inPubMed Google Scholar * Tian-Pei Xie View author publications You can also search for this author inPubMed Google Scholar * Jing Ma View author publications You can also search for

this author inPubMed Google Scholar * Xiao-Ning Wang View author publications You can also search for this author inPubMed Google Scholar * Shu-Guang Wu View author publications You can also

search for this author inPubMed Google Scholar * Donald D. Anthony View author publications You can also search for this author inPubMed Google Scholar * Meng-Chao Wu View author

publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Guo, YJ., Che, XY., Shen, F. _et

al._ Effective tumor vaccines generated by in vitro modification of tumor cells with cytokines and bispecific monoclonal antibodies. _Nat Med_ 3, 451–455 (1997).

https://doi.org/10.1038/nm0497-451 Download citation * Received: 04 December 1996 * Accepted: 11 February 1997 * Issue Date: 01 April 1997 * DOI: https://doi.org/10.1038/nm0497-451 SHARE

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