Combination of radiation and vaccination with autologous tumor cells expressing IL-2, IFN-gamma and GM-CSF for treatment of murine renal carcinoma.
BACKGROUND
We previously showed, in a murine renal cell carcinoma (RCC) model, that lung irradiation plus vaccination with autologous tumor cells producing recombinant interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (Renca/cytokine) reduces the number of lung metastases by over 90%. The present study investigates the host cellular mechanisms mediating this anti-tumor activity.


METHODS
Lung metastases were produced by injection of BALB/c mice i.v. with wild-type Renca cells (wt Renca) on day 0. The mice were then injected s.c. with irradiated Renca/cytokine vaccine cells on days 4, 8 and 11. Lungs were irradiated (300 rads) on day 7. Natural killer (NK) cells or T cells were depleted by injection i.p. with an antibody against anti-asialo GM1 or Thy1.2, respectively. Polyinosinic-polycytidylic acid (poly I:C) was injected i.p. to activate NK cells. Lung tumors were enumerated on day 21.


RESULTS
The anti-asialo GM I antibody totally abolished the antitumor activity elicited by the combined vaccination/radiation treatment regime. In contrast, anti-Thyl.2 antibody did not significantly decrease treatment efficacy. Poly I:C elicited over 95% reduction in lung metastases and strong NK activation as assayed against YAC-1 cells in vitro.


CONCLUSIONS
It appears that NK cells and granulocytes are predominantly involved in the antitumor action elicited by the cytokine-secreting autologous tumor cell vaccine in this metastatic RCC model.
Maini
Atul
A
Department of Urology, SUNY Upstate Medical University, VA Medical Center Syracuse, NY 13210, USA.
Nishisaka
Nobuyasu
N
Kinoshita
Yoshihisa
Y
Jones
Richard F
RF
Wang
Ching Y
CY
Haas
Gabriel P
GP
D000230:Adenocarcinoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005677:G(M1) Ganglioside / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects / Q000528:radiation effects; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000187:drug effects; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology; D011878:Radiotherapy; D013601:T-Lymphocytes / Q000187:drug effects; D018800:Thy-1 Antigens / Q000276:immunology
D019138:Antibodies, Blocking; D019496:Cancer Vaccines; D018800:Thy-1 Antigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D011070:Poly I-C