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A phase‐I clinical study of autologous tumor cells plus interleukin‐2‐gene‐transfected allogeneic fibroblasts as a vaccine in patients with cancer
Author(s) -
Veelken Hendrik,
Mackensen Andreas,
Lahn Michael,
Köhler Gabriele,
Becker Daniel,
Franke Brigitte,
Brennsheidt Ulrich,
Kulmburg Peter,
Rosenthal Felicia M.,
Keller Helmut,
Hasse Joachim,
SchultzeSeemann Wolfgang,
Farthmann Eduard H.,
Mertelsmann Roland,
Lindemann Albrecht
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970127)70:3<269::aid-ijc4>3.0.co;2-v
Subject(s) - cd8 , cytotoxic t cell , medicine , transfection , cancer research , clone (java method) , immunology , immunotherapy , immune system , cell culture , biology , in vitro , dna , biochemistry , genetics
Tumor cells transfected to express immunostimulatory cytokines, or admixed with similarly modified bystander cells, are able to induce immune responses against unmodified tumor cells in animal models. For treatment of human patients, a vaccine composed of autologous tumor cells and IL‐2‐secreting allogeneic fibroblasts was developed. Autologous tumor cells were isolated from biopsy specimens. A clone (KMST6.14) of an immortalized human fibroblast line that stably secreted 5290 IU IL‐2 per 10 6 cells and per 24 hr was obtained by cationic lipofection with an expression construct for human IL‐2 and Neo r . Fifteen patients with refractory malignant tumors received 3–4 injections of irradiated KMST6.14 and autologous tumor cells in a phase‐I clinical trial. Increasing transient inflammatory responses without systemic toxicity developed at vaccination sites and after injections with irradiated tumor cells only ( p < 0.05). These sites contained a dense infiltrate of CD3 + T cells with numbers of CD4 + helper cells exceeding those of CD8 + cytotoxic T cells (CTL). CD8 + T‐cell lines isolated from vaccination sites of 2 malignant melanoma patients but not of renal‐cell carcinoma patients exhibited a dominant lytic activity against autologous tumor cells in vitro . CD8 + T‐cell clones established from the vaccination site of 1 of 2 renal‐cell carcinoma patients preferentially lysed autologous and partially matched allogeneic renal‐cell carcinoma cells. In conclusion, a vaccine composed of IL‐2 gene‐transfected allogeneic fibroblasts and autologous tumor cells is able to enhance specific anti‐tumor T‐cell responses in vivo without major side‐effects. Malignant melanoma and renal‐cell carcinoma appear to be promising entities for testing of similar approaches in future therapeutic trials. Int. J. Cancer , 70:269–277, 1997. © 1997 Wiley‐Liss, Inc.