title: Spleen cells from young but not old immunized mice eradicate large established cancers.
abstract: OBJECTIVE
  Solid tumors that have grown two weeks or longer in mice and have diameters larger than 1 cm are histologically indistinguishable from autochthonous human cancers. When experimental tumors reach this clinically relevant size, they are usually refractory to most immunotherapies but may be destroyed by adoptive T-cell transfer. However, TCR-transgenic T cells and/or tumor cells overexpressing antigens are frequently used in these experiments. Here we studied the requirements for destroying clinical size, unmanipulated 8101 tumors by adoptive cell therapy.
  
  
  METHODS
  8101 arose in an old mouse after chronic exposure to UV light. A cancer line was established, which was never serially transplanted. The immunodominant CD8(+) T cell-recognized antigen of this tumor is caused by a somatic tumor-specific mutation in the RNA helicase p68. 8101 tumors were treated with spleen cells from young naive, or young and old immunized mice to ascertain the characteristics of immune cells that lead to rejection.
  
  
  RESULTS
  Here we show that the mutant p68 peptide has an exceptionally high affinity to the presenting MHC class I molecule K(b) and that spleen cells from immunized young syngeneic mice adoptively transferred to Rag(-/-) or cancer-suppressed euthymic mice eradicate 8101 tumors larger than 1 cm in average diameter and established for several weeks. Spleen cells from naive young mice or from old and boosted (reimmunized) mice were ineffective.
  
  
  CONCLUSIONS
  Relapse-free destruction of large and long-established tumors expressing a genuine very high-affinity tumor-specific antigen can be achieved by using adoptive transfer of lymphocytes from immunized young individuals.
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA. kschrei@uchicago.edu
authors.forename: Karin
authors.initials: K
authors.lastname: Schreiber
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Arina
authors.forename: Boris
authors.initials: B
authors.lastname: Engels
authors.forename: Michael T
authors.initials: MT
authors.lastname: Spiotto
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Karrison
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.forename: Donald A
authors.initials: DA
authors.lastname: Rowley
authors.forename: Hans
authors.initials: H
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D004273:DNA, Neoplasm / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D004273:DNA, Neoplasm