H Büeler1, R C Mulligan. 1. Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts, USA.
Abstract
BACKGROUND: A number of tumors express antigens that are recognized by specific cytotoxic T cells. The normal host immune responses, however, are not usually sufficient to cause tumor rejection. Using appropriate immunization strategies, tumor-specific antigens may serve as targets against which tumor-destructive immune responses can be generated. MAGE-1 and MAGE-3 are two clinically relevant antigens expressed in many human melanomas and other tumors, but not in normal tissues, except testis. Here, we have investigated whether DNA and cellular vaccines against MAGE-1 and MAGE-3 can induce antigen-specific anti-tumor immunity and cause rejection of MAGE-expressing tumors. MATERIALS AND METHODS: Mice were immunized against MAGE-1 and MAGE-3 by subcutaneous injection of genetically modified embryonic fibroblasts or intramuscular injection of purified DNA. Mice were injected with lethal doses of B16 melanoma cells expressing the corresponding MAGE antigens or the unrelated protein SIV tat, and tumor development and survival were monitored. RESULTS: Intramuscular expression of MAGE-1 and MAGE-3 by plasmid DNA injection and subcutaneous immunization with syngeneic mouse embryonic fibroblasts transduced with recombinant retroviruses to express these antigens induced specific immunity against tumors expressing MAGE-1 and MAGE-3. Both CD4+ and CD8+ T cells were required for anti-tumor immunity. Coexpression of granulocyte-macrophage colony-stimulating factor (GM-CSF) or B7-1 significantly increased anti-tumor immunity in an antigen-specific manner and resulted in a considerable proportion of mice surviving lethal tumor challenge. CONCLUSIONS: Our results suggest that genetic and cellular vaccines against MAGE and other tumor antigens may be useful for the therapy of tumors expressing specific markers, and that GM-CSF and B7-1 are potent stimulators for the induction of antigen-specific tumor immunity.
BACKGROUND: A number of tumors express antigens that are recognized by specific cytotoxic T cells. The normal host immune responses, however, are not usually sufficient to cause tumor rejection. Using appropriate immunization strategies, tumor-specific antigens may serve as targets against which tumor-destructive immune responses can be generated. MAGE-1 and MAGE-3 are two clinically relevant antigens expressed in many humanmelanomas and other tumors, but not in normal tissues, except testis. Here, we have investigated whether DNA and cellular vaccines against MAGE-1 and MAGE-3 can induce antigen-specific anti-tumor immunity and cause rejection of MAGE-expressing tumors. MATERIALS AND METHODS:Mice were immunized against MAGE-1 and MAGE-3 by subcutaneous injection of genetically modified embryonic fibroblasts or intramuscular injection of purified DNA. Mice were injected with lethal doses of B16 melanoma cells expressing the corresponding MAGE antigens or the unrelated protein SIV tat, and tumor development and survival were monitored. RESULTS: Intramuscular expression of MAGE-1 and MAGE-3 by plasmid DNA injection and subcutaneous immunization with syngeneic mouse embryonic fibroblasts transduced with recombinant retroviruses to express these antigens induced specific immunity against tumors expressing MAGE-1 and MAGE-3. Both CD4+ and CD8+ T cells were required for anti-tumor immunity. Coexpression of granulocyte-macrophage colony-stimulating factor (GM-CSF) or B7-1 significantly increased anti-tumor immunity in an antigen-specific manner and resulted in a considerable proportion of mice surviving lethal tumor challenge. CONCLUSIONS: Our results suggest that genetic and cellular vaccines against MAGE and other tumor antigens may be useful for the therapy of tumors expressing specific markers, and that GM-CSF and B7-1 are potent stimulators for the induction of antigen-specific tumor immunity.
Authors: W P Fung-Leung; M W Schilham; A Rahemtulla; T M Kündig; M Vollenweider; J Potter; W van Ewijk; T W Mak Journal: Cell Date: 1991-05-03 Impact factor: 41.582
Authors: P van der Bruggen; C Traversari; P Chomez; C Lurquin; E De Plaen; B Van den Eynde; A Knuth; T Boon Journal: Science Date: 1991-12-13 Impact factor: 47.728
Authors: J J Patard; F Brasseur; S Gil-Diez; F Radvanyi; M Marchand; P François; A Abi-Aad; P Van Cangh; C C Abbou; D Chopin Journal: Int J Cancer Date: 1995-02-20 Impact factor: 7.396
Authors: A Rahemtulla; W P Fung-Leung; M W Schilham; T M Kündig; S R Sambhara; A Narendran; A Arabian; A Wakeham; C J Paige; R M Zinkernagel Journal: Nature Date: 1991-09-12 Impact factor: 49.962
Authors: S A Leachman; R E Tigelaar; M Shlyankevich; M D Slade; M Irwin; E Chang; T C Wu; W Xiao; S Pazhani; D Zelterman; J L Brandsma Journal: J Virol Date: 2000-09 Impact factor: 5.103
Authors: G F Hofbauer; C Schaefer; C Noppen; R Böni; J Kamarashev; F O Nestle; G C Spagnoli; R Dummer Journal: Am J Pathol Date: 1997-12 Impact factor: 4.307
Authors: Xiao-Lin Li; Marjolein Sluijter; Elien M Doorduijn; Shubha P Kale; Harris McFerrin; Yong-Yu Liu; Yan Li; Madhusoodanan Mottamal; Xin Yao; Fengkun Du; Baihan Gu; Kim Hoang; Yen H Nguyen; Nichelle Taylor; Chelsea R Stephens; Thorbald van Hall; Qian-Jin Zhang Journal: PLoS One Date: 2014-11-10 Impact factor: 3.240