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Lentivector immunization induces tumor antigen‐specific B and T cell responses in vivo
Author(s) -
Garcia Casado Javier,
Janda Jozef,
Wei Joe,
Chapatte Laurence,
Colombetti Sara,
Alves Pedro,
Ritter Gerd,
Ayyoub Maha,
Valmori Danila,
Chen Weisan,
Lévy Frédéric
Publication year - 2008
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200737923
Subject(s) - biology , immune system , antigen , cd8 , cytotoxic t cell , epitope , in vivo , t cell , immunology , immunization , tumor antigen , ex vivo , immunotherapy , in vitro , biochemistry , microbiology and biotechnology
Abstract Expression of the cancer/germ‐line antigen NY‐ESO‐1 by tumors elicits spontaneous humoral and cellular immune responses in some cancer patients. Development of vaccines capable of stimulating such comprehensive immune responses is desirable. We have produced recombinant lentivectors directing the intracellular synthesis of NY‐ESO‐1 (rLV/ESO) and have analyzed the in vivo immune response elicited by this vector. Single injection of rLV/ESO into HLA‐A2‐transgenic mice elicited long‐lasting B and T cell responses against NY‐ESO‐1. CD8 + T cells against the HLA‐A2‐restricted peptide NY‐ESO‐1 157–165 were readily detectable ex vivo and showed restricted TCR Vβ usage. Moreover, rLV/ESO elicited a far greater anti‐NY‐ESO‐1 157–165 CD8 + T cell response than peptide‐ or protein‐based vaccines. Anti‐NY‐ESO‐1 antibodies were rapidly induced after immunization and their detection preceded that of the antigen‐specific CD8 + T cells. The rLV/ESO also induced CD4 + T cells. These cells played an essential role as their depletion completely abrogated B cell and CD8 + T cell responses against NY‐ESO‐1. The induced CD4 + T cells were primarily directed against a single NY‐ESO‐1 epitope spanning amino acids 81–100. Altogether, our study shows that rLV/ESO induces potent and comprehensive immune responses in vivo .