Combination of radiation and vaccination with autologous tumor cells expressing IL-2, IFN-gamma and GM-CSF for treatment of murine renal carcinoma.

Abstract

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.

MATERIALS AND 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.

• Authors: Atul Maini, Nobuyasu Nishisaka, Yoshihisa Kinoshita, Richard F Jones, Ching Y Wang, Gabriel P Haas
• Journal: In vivo (Athens, Greece) (In Vivo) 2003 Mar-Apr Vol. 17 Issue 2 Pg. 119-23 ISSN: 0258-851X [Print] Greece
• PMID: 12792971 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Blocking
• Cancer Vaccines
• Thy-1 Antigens
• G(M1) Ganglioside
• asialo GM1 ganglioside
• Poly I-C

Topics

• Adenocarcinoma (immunology, secondary, therapy)
• Animals
• Antibodies, Blocking (pharmacology)
• Cancer Vaccines (administration & dosage, pharmacology, therapeutic use)
• Carcinoma, Renal Cell (immunology, pathology, therapy)
• Cell Line, Tumor
• Combined Modality Therapy
• G(M1) Ganglioside (immunology)
• Immunity, Cellular (drug effects, radiation effects)
• Injections, Intraperitoneal
• Injections, Subcutaneous
• Killer Cells, Natural (drug effects)
• Lung Neoplasms (immunology, secondary, therapy)
• Mice
• Mice, Inbred BALB C
• Poly I-C (administration & dosage, pharmacology)
• Radiotherapy
• T-Lymphocytes (drug effects)
• Thy-1 Antigens (immunology)