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A pilot study of combined immunotherapy with autologous adoptive tumour‐specific T‐cell transfer, vaccination with CD40‐activated malignant B cells and interleukin 2
Author(s) -
Schultze J. L.,
Anderson K. C.,
Gilleece M. H.,
Gribben J. G.,
Nadler L. M.
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02760.x
Subject(s) - adoptive cell transfer , ex vivo , immunotherapy , medicine , cd40 , immunology , t cell , cell therapy , cytotoxic t cell , interleukin 2 , stem cell , cancer research , in vivo , biology , immune system , in vitro , biochemistry , genetics , microbiology and biotechnology
Most B‐cell malignancies are incurable diseases and therefore warrant new therapeutic approaches. In a pilot study, we tested the feasibility and safety of combined immunotherapy consisting of adoptive transfer of autologous tumour‐specific T cells, low‐dose interleukin 2 (IL‐2) and a cellular vaccine of CD40‐activated plasma cell leukaemia (PCL) cells in a patient who failed tandem repeat stem cell transplantation and idiotype vaccination. Autologous tumour‐specific T cells for adoptive T‐cell transfer were propagated in vitro by repetitive stimulation with autologous ex vivo CD40‐activated PCL cells. CD40‐activated PCL cells for vaccination were similarly generated ex vivo by co‐culture with CD40 ligand transfectants. Autologous T cells (5 × 10 8 and 2·5 × 10 9 for two separate treatment cycles) generated ex vivo and cytotoxic against autologous tumours were infused and well tolerated by the patient. Fever and myalgias were closely related to IL‐2 injections and no other adverse effects were observed. A temporary decrease of PCL cells in peripheral blood was seen after the first cycle of adoptive T‐cell therapy, tumour cell vaccination and low‐dose IL‐2. Tumour progression was associated with tumour cells that (1) expressed a complex karyotype, (2) demonstrated loss of MHC class II, and (3) did not induce autologous tumour‐specific T‐cell lines ex vivo . We demonstrated the safety and feasibility in combining autologous tumour‐specific T‐cell therapy with low‐dose IL‐2 and that clinical trials based on the use of CD40‐activated autologous tumour cell vaccines are warranted in patients with CD40‐activated autologous tumour cells, either as a vaccine or for ex vivo stimulation of autologous T cells.