Immunotherapy with cytokine induced killer cells in solid and hematopoietic tumours: a pilot clinical trial.
OBJECTIVE
CIK cells are a novel population of efficient immune effector cells with high antitumour activity mainly due to the high proliferation of CD3(+)CD56(+) cells, so may play a role in the development of new forms of adoptive cellular immunotherapy. We started a pilot clinical trial with autologous CIK cells in patients with refractory lymphoma and metastatic solid tumours. This study was aimed at determining the feasibility of generating a sufficient number of CIK cells in heavily pretreated patients and at assessing treatment toxicity.


METHODS
CIK cells were generated from peripheral blood mononuclear cells (MNC) and incubated in the presence of IFN-gamma followed by OKT3 and IL-2. Treatment schedule consisted of three cycles of CIK cells infusions at an interval of 3 weeks.


RESULTS
At present 12 patients were enrolled: 6 advanced lymphomas, 5 metastatic kidney carcinoma and 1 hepatocellular carcinoma (HCC). The median number of transferred cells per patient was 28 x 10(9) (range, 6-61). Protocol adherence was excellent and the toxicity profile was favourable. After CIK cells infusion, the absolute median count of lymphocytes, CD3(+), CD8(+) and CD3(+)CD56(+) cells significantly increased in patient's peripheral blood. Clinical outcome appeared promising: three patients had complete response (CR) and two patients had stabilization of disease with a median follow-up of 33 months (range, 9-44).


CONCLUSIONS
These preliminary data showed that adoptive immunotherapy with CIK cells is a safe therapy with some suggestion of efficacy that significantly enhances immune functions increasing absolute numbers of effector cells without side effects. If confirmed in larger scale studies, these promising results may have a favourable impact on conventional treatment strategy of malignancies.
Olioso
Paola
P
Terapia Intensiva Ematologica per il Trapianto Emopoietico, Dipartimento di Medicina Trasfusionale, Laboratorio di Terapia Cellulare, Ospedale Civile"Spirito Santo, 65124 Pescara, Italy. paolioso@tin.it
Giancola
Raffaella
R
Di Riti
Maria
M
Contento
Alessandro
A
Accorsi
Patrizia
P
Iacone
Antonio
A
D000328:Adult; D000368:Aged; D001804:Blood Transfusion, Autologous; D002277:Carcinoma / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D017708:Leukocyte Transfusion / Q000009:adverse effects; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008223:Lymphoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
D016207:Cytokines