Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial.
Adoptive immunotherapy (AIT) of cancer with T lymphocytes may be limited by the need to activate tumor antigen-sensitized cells in vitro. In murine models, we have shown that AIT with tumor-sensitized T cells that have been pharmacologically activated with bryostatin 1 and ionomycin plus interleukin-2 can induce tumor regression. A Phase I clinical trial was carried out to assess the feasibility and toxicity associated with using tumor- or vaccine-draining lymph node cells, activated pharmacologically and expanded in culture with low-dose interleukin-2 and infused intravenously, followed by IL-2 infusion. Nine patients were entered into the trial, and six were treated as planned. Average expansion of cell numbers over 13 to 27 days in culture was 118-fold. No patient's cells reached the target cell number (2.5 x 10(10)). Infusion of these cells did not result in any unexpected toxicities. The toxicities observed were related to IL-2 infusion, and conformed to the expected range of side-effects. Based on these Phase I results, additional trials, with tumor antigen vaccine-sensitized DLN and technical modifications of the culture technique, are planned.
Bear
H D
HD
Massey Cancer Center, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA. hbear@hsc.vcu.edu
Roberts
J
J
Cornell
D
D
Tombes
M B
MB
Kyle
B
B
D000328:Adult; D054713:Bryostatins; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D018942:Macrolides; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000187:drug effects / Q000637:transplantation*
D054713:Bryostatins; D007376:Interleukin-2; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D015759:Ionomycin