Induction of immunity to prostate cancer antigens: Results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer
Jw. Simons et al., Induction of immunity to prostate cancer antigens: Results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer, CANCER RES, 59(20), 1999, pp. 5160-5168
Vaccination with irradiated granulocyte-macrophage colony-stimulating facto
r (GM-CSF)-secreting gene-transduced cancer vaccines induces tumoricidal im
mune responses, In a Phase I human gene therapy trial, eight immunocompeten
t prostate cancer (PCA) patients were treated with autologous, GM-CSF-secre
ting, irradiated tumor vaccines prepared from ex vivo retroviral transducti
on of surgically harvested cells. Expansion of primary cultures of autologo
us vaccine cells was successful to meet trial specifications in 8 of 11 cas
es (73%); the yields of the primary culture cell limited the number of cour
ses of vaccination. Side effects were pruritis, erythema, and swelling at v
accination sites. Vaccine site biopsies manifested infiltrates of dendritic
cells and macrophages among prostate tumor vaccine cells, Vaccination acti
vated new T-cell and B-cell immune responses against PCA antigens. T-cell r
esponses, evaluated by assessing delayed-type hypersensitivity (DTH) reacti
ons against untransduced autologous tumor cells, were evident in two of eig
ht patients before vaccination and in seven of eight patients after treatme
nt. Reactive DTH site biopsies manifested infiltrates of effector cells con
sisting of CD45RO+ T-cells, and degranulating eosinophils consistent with a
ctivation of both Th1 and Th2 T-cell responses. A distinctive eosinophilic
vasculitis was evident near autologous tumor cells at vaccine sites, and at
DTH sites. B-cell responses were also induced. Sera from three of eight va
ccinated men contained new antibodies recognizing polypeptides of 26, 31, a
nd 150 kDa in protein extracts from prostate cells, The 150-kDa polypeptide
was expressed by LNCaP and PC-3 PCA cells, as web as by normal prostate ep
ithelial cells, but not by prostate stromal cells. No antibodies against pr
ostate-specific antigen were detected. These data suggest that both T-cell
and B-cell immune responses to human PCA can be generated by treatment with
irradiated, GM-CSF gene-transduced PCB vaccines.