Hd. Bear et al., Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial, CANCER IMMU, 50(5), 2001, pp. 269-274
Adoptive immunotherapy (AIT) of cancer with T lymphocytes may be limited by
the need to activate tumor antigen-sensitized cells in vitro. In murine mo
dels, we have shown that AIT with tumor-sensitized T cells that have been p
harmacologically activated with bryostatin I 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 vaccin
e-draining lymph node cells, activated pharmacologically and expanded in cu
lture with low-dose interleukin-2 and infused intravenously, followed by IL
-2 infusion. Nine patients were entered into the trial, and six were treate
d as planned. Average expansion of cell numbers over 13 to 27 days in cultu
re was 118-fold. No patient's cells reached the target cell number (2.5 x 1
0(10)). Infusion of these cells did not result in any unexpected toxicities
. The toxicities observed were related to IL-2 infusion, and conformed to t
he expected range of side-effects. Based on these Phase I results, addition
al trials, with tumor antigen vaccine-sensitized DLN and technical modifica
tions of the culture technique, are planned.