Pulmonary metastases neutralization and tumor rejection by in vivo administration of β glucan and bispecific antibody

Christophe Penna, Phillip A. Dean, Heidi Nelson

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant β glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with C1-62 melanoma cells and immediately treated with i.p. β glucan and/or anti-CD3 (500AZ) x anti p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with C1-62 cells and 7 days later administered β glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the β glucan + BsAb group, as compared with controls, and with β glucan alone. In the established tumor model, β glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with β glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and β glucan alone. We conclude that T cells can be activated in vivo by β glucan and retargeted with F(ab')2 BsAb.

Original languageEnglish (US)
Pages (from-to)377-382
Number of pages6
JournalInternational Journal of Cancer
Volume65
Issue number3
DOIs
StatePublished - Jan 26 1996

Fingerprint

Bispecific Antibodies
Glucans
Neoplasm Metastasis
Lung
Neoplasms
T-Lymphocytes
Neutralization Tests
Antibody Specificity
Inbred C3H Mouse
Surface Antigens
Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pulmonary metastases neutralization and tumor rejection by in vivo administration of β glucan and bispecific antibody. / Penna, Christophe; Dean, Phillip A.; Nelson, Heidi.

In: International Journal of Cancer, Vol. 65, No. 3, 26.01.1996, p. 377-382.

Research output: Contribution to journalArticle

@article{e1cd9d5cb51242259ad98a57af26ccf9,
title = "Pulmonary metastases neutralization and tumor rejection by in vivo administration of β glucan and bispecific antibody",
abstract = "Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant β glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with C1-62 melanoma cells and immediately treated with i.p. β glucan and/or anti-CD3 (500AZ) x anti p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with C1-62 cells and 7 days later administered β glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the β glucan + BsAb group, as compared with controls, and with β glucan alone. In the established tumor model, β glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with β glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and β glucan alone. We conclude that T cells can be activated in vivo by β glucan and retargeted with F(ab')2 BsAb.",
author = "Christophe Penna and Dean, {Phillip A.} and Heidi Nelson",
year = "1996",
month = "1",
day = "26",
doi = "10.1002/(SICI)1097-0215(19960126)65:3<377::AID-IJC17>3.0.CO;2-7",
language = "English (US)",
volume = "65",
pages = "377--382",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Pulmonary metastases neutralization and tumor rejection by in vivo administration of β glucan and bispecific antibody

AU - Penna, Christophe

AU - Dean, Phillip A.

AU - Nelson, Heidi

PY - 1996/1/26

Y1 - 1996/1/26

N2 - Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant β glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with C1-62 melanoma cells and immediately treated with i.p. β glucan and/or anti-CD3 (500AZ) x anti p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with C1-62 cells and 7 days later administered β glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the β glucan + BsAb group, as compared with controls, and with β glucan alone. In the established tumor model, β glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with β glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and β glucan alone. We conclude that T cells can be activated in vivo by β glucan and retargeted with F(ab')2 BsAb.

AB - Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant β glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with C1-62 melanoma cells and immediately treated with i.p. β glucan and/or anti-CD3 (500AZ) x anti p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with C1-62 cells and 7 days later administered β glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the β glucan + BsAb group, as compared with controls, and with β glucan alone. In the established tumor model, β glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with β glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and β glucan alone. We conclude that T cells can be activated in vivo by β glucan and retargeted with F(ab')2 BsAb.

UR - http://www.scopus.com/inward/record.url?scp=0030044851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030044851&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0215(19960126)65:3<377::AID-IJC17>3.0.CO;2-7

DO - 10.1002/(SICI)1097-0215(19960126)65:3<377::AID-IJC17>3.0.CO;2-7

M3 - Article

C2 - 8575861

AN - SCOPUS:0030044851

VL - 65

SP - 377

EP - 382

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -