title: Isolation and in vitro expansion of lymphocytes infiltrating non-small cell lung carcinoma: functional and molecular characterisation for their use in adoptive immunotherapy.
abstract: Tumour infiltrating lymphocytes (TIL) have the capability of recognising and lysing autologous cancer cells, both in vitro and in vivo. Advanced non-small cell lung carcinoma (NSCLC) is partially insensitive to chemo radiotherapy and has a poor prognosis: thus, for this, an immunotherapeutic approach could be attempted. We expanded in vitro 46 out of 70 samples of TIL derived from NSCLC. From proliferating TILS, a number varying from 10 to 50 x 10(9) cells was obtained. These lymphocytes belonged to the T cell lineage, had the capability of growing for 45-60 days and lysed autologous better than allogeneic cancer cells. In addition, analysis of the restriction maps of T cell receptor (TRC)-beta, demonstrated that an oligoclonal population of T cells was preselected in vivo, near the tumour site, and might be expanded in vivo, using phytohaemagglutin and interleukin 2 while maintaining the same characteristics of the original population. These results give a clear rationale for the use of in vitro expanded TIL from NSCLC in protocols of adoptive immunotherapy in patients with residual disease following surgery.
authors.affiliation: Servizio di Patologia Clinica, Istituto Nazionale per la Ricerca sul Cancro Viale Benedetto XV, Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Melioli
authors.forename: G
authors.initials: G
authors.lastname: Ratto
authors.forename: M
authors.initials: M
authors.lastname: Guastella
authors.forename: M
authors.initials: M
authors.lastname: Meta
authors.forename: R
authors.initials: R
authors.lastname: Biassoni
authors.forename: C
authors.initials: C
authors.lastname: Semino
authors.forename: G
authors.initials: G
authors.lastname: Casartelli
authors.forename: W
authors.initials: W
authors.lastname: Pasquetti
authors.forename: A
authors.initials: A
authors.lastname: Catrullo
authors.forename: L
authors.initials: L
authors.lastname: Moretta
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015183:Restriction Mapping; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell