Gene therapy with autologous, interleukin 2-secreting tumor cells in patients with malignant melanoma.
We vaccinated metastatic melanoma patients with irradiated, autologous melanoma cells genetically engineered to secrete interleukin 2 (IL-2) to investigate whether an anti-tumor immune response would be induced. Melanoma cell cultures were established from surgical specimens and were engineered to secrete IL-2 by infection with recombinant retrovirus. Twelve patients were vaccinated subcutaneously one, two, or three times with approximately 10(7) irradiated, autologous, IL-2-secreting tumor cells. Treatment was well tolerated, with local reactions at 11 of 24 injection sites and minor systemic symptoms of fever and headache after 6 injections. One patient developed anti-tumor DTH after the first vaccination and showed an increased response after the second vaccination. Anti-autologous tumor CTLs could be detected prevaccination in the peripheral blood of seven patients and their activity increased after vaccination in four patients. No UICC-defined clinical responses were seen, but three patients had stable disease for 7-15 months, one of whom has not yet progressed (15+ months). Thus, patient vaccination with autologous, genetically engineered tumor cells is feasible and safe. Anti-tumor DTH and CTLs can be induced in some patients with such a vaccine.
Palmer
K
K
CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, London, UK.
Moore
J
J
Everard
M
M
Harris
J D
JD
Rodgers
S
S
Rees
R C
RC
Murray
A K
AK
Mascari
R
R
Kirkwood
J
J
Riches
P G
PG
Fisher
C
C
Thomas
J M
JM
Harries
M
M
Johnston
S R
SR
Collins
M K
MK
Gore
M E
ME
D000328:Adult; D019496:Cancer Vaccines / Q000276:immunology*; D017690:Cell Transplantation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D014182:Transplantation, Autologous; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D019496:Cancer Vaccines; D007376:Interleukin-2; D019444:Vaccines, DNA