TY - JOUR
T1 - Immunogenicity of the tumor determines the outcome of immunotherapy with interleukin-2, ABPP, and cyclophosphamide of micro- and macrometastatic intraperitoneal tumor.
AU - Eggermont, A. M.
AU - Sugarbaker, P. H.
PY - 1990
Y1 - 1990
N2 - We have shown previously that interleukin-2 (IL-2) and the interferon inducer ABPP can induce lymphokine activated killer (LAK) cell activity in vivo after intraperitoneal (i.p.) administration. The antitumor effects of various immunotherapy regimens with IL-2, LAK cells, ABPP, and cyclophosphamide (CY) on microscopic (day 3) and on macroscopic (day 8) i.p. tumors, differing in histology and immunogenicity, were studied in C57BL6 mice. The immunogenic sarcomas MCA-105, -106, and the colon adenocarcinoma MCA-38, and the nonimmunogenic sarcomas MCA-101, -102 were used. After i.p. inoculation of 1 X 10(5) tumor cells i.p. on day 0, therapy with IL-2 +/- LAK cells consisted of 1 X 10(8) LAK cells, i.p., on day 3 and IL-2, 10k to 25k U, i.p., b.i.d., on days 3 to 7. Treatment with ABPP +/- CY consisted of CY, 50 mg/kg, i.p., on day 3 and/or 8 ABPP, 250 mg/kg on days 3, 4 and/or 8, 9. In the treatment of micrometastases, IL-2 + LAK cell therapy was effective against all tumors. Therapy with low dose IL-2 alone was effective only against immunogenic tumors. Combined therapy with CY was very effective against the immunogenic tumors and prolonged survival significantly. Only marginal antitumor effects were seen against nonimmunogenic tumors. In the setting of advanced tumor, chemoimmunotherapy was only successful against immunogenic tumors. These observations demonstrate that the immunogenicity of the tumor is of major importance in the outcome of immunotherapy, especially in the setting of advanced disease. This indicates that, apart from LAK cells, the in vivo activation of other cytotoxic effector cells is important in the rejection of immunogenic tumors.
AB - We have shown previously that interleukin-2 (IL-2) and the interferon inducer ABPP can induce lymphokine activated killer (LAK) cell activity in vivo after intraperitoneal (i.p.) administration. The antitumor effects of various immunotherapy regimens with IL-2, LAK cells, ABPP, and cyclophosphamide (CY) on microscopic (day 3) and on macroscopic (day 8) i.p. tumors, differing in histology and immunogenicity, were studied in C57BL6 mice. The immunogenic sarcomas MCA-105, -106, and the colon adenocarcinoma MCA-38, and the nonimmunogenic sarcomas MCA-101, -102 were used. After i.p. inoculation of 1 X 10(5) tumor cells i.p. on day 0, therapy with IL-2 +/- LAK cells consisted of 1 X 10(8) LAK cells, i.p., on day 3 and IL-2, 10k to 25k U, i.p., b.i.d., on days 3 to 7. Treatment with ABPP +/- CY consisted of CY, 50 mg/kg, i.p., on day 3 and/or 8 ABPP, 250 mg/kg on days 3, 4 and/or 8, 9. In the treatment of micrometastases, IL-2 + LAK cell therapy was effective against all tumors. Therapy with low dose IL-2 alone was effective only against immunogenic tumors. Combined therapy with CY was very effective against the immunogenic tumors and prolonged survival significantly. Only marginal antitumor effects were seen against nonimmunogenic tumors. In the setting of advanced tumor, chemoimmunotherapy was only successful against immunogenic tumors. These observations demonstrate that the immunogenicity of the tumor is of major importance in the outcome of immunotherapy, especially in the setting of advanced disease. This indicates that, apart from LAK cells, the in vivo activation of other cytotoxic effector cells is important in the rejection of immunogenic tumors.
UR - http://www.scopus.com/inward/record.url?scp=0024988619&partnerID=8YFLogxK
M3 - Article
C2 - 2224911
AN - SCOPUS:0024988619
SN - 0361-090X
VL - 14
SP - 483
EP - 490
JO - Cancer detection and prevention
JF - Cancer detection and prevention
IS - 4
ER -