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Selective antibody‐mediated targeting of class I MHC to EGFR‐expressing tumor cells induces potent antitumor CTL activity in vitro and in vivo
Author(s) -
Novak Hila,
Noy Roy,
Oved Kfir,
Segal Dina,
Wels Winfried S.,
Reiter Yoram
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22168
Subject(s) - ctl* , in vivo , in vitro , cancer research , mhc class i , antibody , immunology , biology , major histocompatibility complex , cytotoxic t cell , chemistry , antigen , biochemistry , genetics
Epidermal growth factor receptor (EGFR) is highly overexpressed in many tumor types. We present a new fusion molecule that can target solid tumors that express EGFR. The fusion molecule combines the advantage(s) of the well‐established tumor targeting capabilities of high affinity recombinant fragments of antibodies with the known efficient, specific and potent killing ability of CD8 T lymphocytes directed against highly antigenic MHC/peptide complexes. A recombinant chimeric molecule was created by the genetic fusion of the scFv antibody fragment derived from the anti‐EGFR monoclonal antibody C225, to monomeric single‐chain HLA‐A2 complexes containing immunodominant tumor or viral‐specific peptides. The fusion protein can induce very efficiently CTL‐dependent lysis of EGFR‐expressing tumor cells regardless of the expression of self peptide‐MHC complexes. Moreover, the molecule exhibited very potent antitumor activity in vivo in nude mice bearing preestablished human tumor xenografts. These in vitro and in vivo results indicate that recombinant scFv‐MHC‐peptide fusion molecules might represent a novel and powerful approach to immunotherapy of solid tumors, bridging antibody and T lymphocyte attack on cancer cells. © 2006 Wiley‐Liss, Inc.