Isolation and in vitro expansion of lymphocytes infiltrating non-small cell lung carcinoma: functional and molecular characterisation for their use in adoptive immunotherapy.
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.
Melioli
G
G
Servizio di Patologia Clinica, Istituto Nazionale per la Ricerca sul Cancro Viale Benedetto XV, Genova, Italy.
Ratto
G
G
Guastella
M
M
Meta
M
M
Biassoni
R
R
Semino
C
C
Casartelli
G
G
Pasquetti
W
W
Catrullo
A
A
Moretta
L
L
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
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell