Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor β antibody and interleukin-2

Slawomir Wojtowicz-Praga, Udit M. Verma, Lalage Wakefield, Jose M. Esteban, Dan Hartmann, Amitabha Mazumder

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Earlier evidence suggests that transforming growth factor β (TGFβ) plays a significant role in tumor progression and metastasis. The most likely mechanism of the action of TGFβ is induction of immunosuppression in the host, allowing for unchecked tumor growth and metastasis. We attempted to test that hypothesis and to compare antitumor effects of anti-TGFβ antibody alone and in combination with interleukin-2 (IL-2). Six- to 8-week-old female C57B1-6 mice were induced with murine B16 melanoma by tail vein injection. Therapy was started 48 h after tumor injections. Monoclonal anti-TGFβ antibody (2G7) was administered intraperitoneally (i.p.) at 500 μg every other day, and IL-2 at 10,000 U i.p. twice daily, for 21 days. A threefold decrease in the number of lesions in the anti-TGFβ/IL-2 treatment group compared with the control group was observed, a highly significant statistical difference (p = 0.002). No statistically significant differences were seen between the control group and other studied groups (IL-2 alone, anti-TGFβ alone). Analysis of TGFβ levels in plasma by the TGFβ-1 Quantikine assay indicated normal levels in the control and IL-2 groups, and significantly diminished levels in the two groups that received TGFβ antibody. However, acid-ethanol extraction of plasma (to reverse antibody binding before assay) showed normal plasma TGFβ levels in all groups, suggesting that the antibody may alter the availability of TGFβ in vivo. Microscopic analysis of metastases revealed a decrease in the average size of lesions in the groups treated with IL-2. Thus, combination therapy using anti-TGFβ antibody and IL-2 may be a novel, less toxic approach to tumor immunotherapy.

Original languageEnglish (US)
Pages (from-to)169-175
Number of pages7
JournalJournal of Immunotherapy
Volume19
Issue number3
DOIs
StatePublished - 1996

Fingerprint

Experimental Melanomas
Transforming Growth Factors
Interleukin-2
Neoplasm Metastasis
Antibodies
Growth
Neoplasms
Control Groups
Injections
Poisons
Immunotherapy
Immunosuppression
Tail
Veins
Ethanol
Therapeutics

Keywords

  • 1L-2
  • Cancer
  • Cytokines
  • Immunosuppression
  • Melanoma
  • Metastasis
  • TGFβ

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor β antibody and interleukin-2. / Wojtowicz-Praga, Slawomir; Verma, Udit M.; Wakefield, Lalage; Esteban, Jose M.; Hartmann, Dan; Mazumder, Amitabha.

In: Journal of Immunotherapy, Vol. 19, No. 3, 1996, p. 169-175.

Research output: Contribution to journalArticle

Wojtowicz-Praga, Slawomir ; Verma, Udit M. ; Wakefield, Lalage ; Esteban, Jose M. ; Hartmann, Dan ; Mazumder, Amitabha. / Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor β antibody and interleukin-2. In: Journal of Immunotherapy. 1996 ; Vol. 19, No. 3. pp. 169-175.
@article{e3b5872fa72c496c925d7eaa7d68210b,
title = "Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor β antibody and interleukin-2",
abstract = "Earlier evidence suggests that transforming growth factor β (TGFβ) plays a significant role in tumor progression and metastasis. The most likely mechanism of the action of TGFβ is induction of immunosuppression in the host, allowing for unchecked tumor growth and metastasis. We attempted to test that hypothesis and to compare antitumor effects of anti-TGFβ antibody alone and in combination with interleukin-2 (IL-2). Six- to 8-week-old female C57B1-6 mice were induced with murine B16 melanoma by tail vein injection. Therapy was started 48 h after tumor injections. Monoclonal anti-TGFβ antibody (2G7) was administered intraperitoneally (i.p.) at 500 μg every other day, and IL-2 at 10,000 U i.p. twice daily, for 21 days. A threefold decrease in the number of lesions in the anti-TGFβ/IL-2 treatment group compared with the control group was observed, a highly significant statistical difference (p = 0.002). No statistically significant differences were seen between the control group and other studied groups (IL-2 alone, anti-TGFβ alone). Analysis of TGFβ levels in plasma by the TGFβ-1 Quantikine assay indicated normal levels in the control and IL-2 groups, and significantly diminished levels in the two groups that received TGFβ antibody. However, acid-ethanol extraction of plasma (to reverse antibody binding before assay) showed normal plasma TGFβ levels in all groups, suggesting that the antibody may alter the availability of TGFβ in vivo. Microscopic analysis of metastases revealed a decrease in the average size of lesions in the groups treated with IL-2. Thus, combination therapy using anti-TGFβ antibody and IL-2 may be a novel, less toxic approach to tumor immunotherapy.",
keywords = "1L-2, Cancer, Cytokines, Immunosuppression, Melanoma, Metastasis, TGFβ",
author = "Slawomir Wojtowicz-Praga and Verma, {Udit M.} and Lalage Wakefield and Esteban, {Jose M.} and Dan Hartmann and Amitabha Mazumder",
year = "1996",
doi = "10.1097/00002371-199605000-00001",
language = "English (US)",
volume = "19",
pages = "169--175",
journal = "Journal of Immunotherapy",
issn = "1524-9557",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor β antibody and interleukin-2

AU - Wojtowicz-Praga, Slawomir

AU - Verma, Udit M.

AU - Wakefield, Lalage

AU - Esteban, Jose M.

AU - Hartmann, Dan

AU - Mazumder, Amitabha

PY - 1996

Y1 - 1996

N2 - Earlier evidence suggests that transforming growth factor β (TGFβ) plays a significant role in tumor progression and metastasis. The most likely mechanism of the action of TGFβ is induction of immunosuppression in the host, allowing for unchecked tumor growth and metastasis. We attempted to test that hypothesis and to compare antitumor effects of anti-TGFβ antibody alone and in combination with interleukin-2 (IL-2). Six- to 8-week-old female C57B1-6 mice were induced with murine B16 melanoma by tail vein injection. Therapy was started 48 h after tumor injections. Monoclonal anti-TGFβ antibody (2G7) was administered intraperitoneally (i.p.) at 500 μg every other day, and IL-2 at 10,000 U i.p. twice daily, for 21 days. A threefold decrease in the number of lesions in the anti-TGFβ/IL-2 treatment group compared with the control group was observed, a highly significant statistical difference (p = 0.002). No statistically significant differences were seen between the control group and other studied groups (IL-2 alone, anti-TGFβ alone). Analysis of TGFβ levels in plasma by the TGFβ-1 Quantikine assay indicated normal levels in the control and IL-2 groups, and significantly diminished levels in the two groups that received TGFβ antibody. However, acid-ethanol extraction of plasma (to reverse antibody binding before assay) showed normal plasma TGFβ levels in all groups, suggesting that the antibody may alter the availability of TGFβ in vivo. Microscopic analysis of metastases revealed a decrease in the average size of lesions in the groups treated with IL-2. Thus, combination therapy using anti-TGFβ antibody and IL-2 may be a novel, less toxic approach to tumor immunotherapy.

AB - Earlier evidence suggests that transforming growth factor β (TGFβ) plays a significant role in tumor progression and metastasis. The most likely mechanism of the action of TGFβ is induction of immunosuppression in the host, allowing for unchecked tumor growth and metastasis. We attempted to test that hypothesis and to compare antitumor effects of anti-TGFβ antibody alone and in combination with interleukin-2 (IL-2). Six- to 8-week-old female C57B1-6 mice were induced with murine B16 melanoma by tail vein injection. Therapy was started 48 h after tumor injections. Monoclonal anti-TGFβ antibody (2G7) was administered intraperitoneally (i.p.) at 500 μg every other day, and IL-2 at 10,000 U i.p. twice daily, for 21 days. A threefold decrease in the number of lesions in the anti-TGFβ/IL-2 treatment group compared with the control group was observed, a highly significant statistical difference (p = 0.002). No statistically significant differences were seen between the control group and other studied groups (IL-2 alone, anti-TGFβ alone). Analysis of TGFβ levels in plasma by the TGFβ-1 Quantikine assay indicated normal levels in the control and IL-2 groups, and significantly diminished levels in the two groups that received TGFβ antibody. However, acid-ethanol extraction of plasma (to reverse antibody binding before assay) showed normal plasma TGFβ levels in all groups, suggesting that the antibody may alter the availability of TGFβ in vivo. Microscopic analysis of metastases revealed a decrease in the average size of lesions in the groups treated with IL-2. Thus, combination therapy using anti-TGFβ antibody and IL-2 may be a novel, less toxic approach to tumor immunotherapy.

KW - 1L-2

KW - Cancer

KW - Cytokines

KW - Immunosuppression

KW - Melanoma

KW - Metastasis

KW - TGFβ

UR - http://www.scopus.com/inward/record.url?scp=0030036344&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030036344&partnerID=8YFLogxK

U2 - 10.1097/00002371-199605000-00001

DO - 10.1097/00002371-199605000-00001

M3 - Article

C2 - 8811491

AN - SCOPUS:0030036344

VL - 19

SP - 169

EP - 175

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1524-9557

IS - 3

ER -