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PNAS June 15, 2004 vol. 101 no. 24 9051-9056

ImmunologyTumor-specific Ab-mediated targeting of MHC-peptide complexes induces regression of human tumor xenografts in vivo
Avital Lev * , Roy Noy * , Kfir Oved *, Hila Novak *, Dina Segal *, Peter Walden , Dietmar Zehn and Yoram Reiter *,
*Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; and Department of Dermatology, Medical School Charite, Humboldt University, D-10117 Berlin, Germany
Communicated by Lloyd J. Old, Ludwig Institute for Cancer Research, New York, NY, May 7, 2004 (received for review January 19, 2004)
A cancer immunotherapy strategy is described herein that combines the advantage of the well established tumor targeting capabilities of high-affinity recombinant fragments of Abs with the known efficient, specific, and potent killing ability of CD8 T lymphocytes directed against highly antigenic MHC-peptide complexes. Structurally, it consists of a previously uncharacterized class of recombinant chimerical molecules created by the genetic fusion of single-chain (sc) Fv Ab fragments, specific for tumor cell surface antigens, to monomeric scHLA-A2 complexes containing immunodominant tumor- or viral-specific peptides. The fusion protein can induce very efficiently tumor cell lysis, regardless of the expression of self peptide-MHC complexes. Moreover, these molecules exhibited very potent antitumor activity in vivo in nude mice bearing preestablished human tumor xenografts. These in vitro and in vivo results suggest that recombinant scFv-MHC-peptide fusion molecules could represent an approach to immunotherapy, bridging Ab and T lymphocyte attack on cancer cells.