T cell activation and retargeting using staphylococcal enterotoxin B and bispecific antibody: An effective in vivo antitumor strategy

Lewis E. Porter, Heidi Nelson, I. Ethem Gecim, David C. Rice, Claude Thibault, Andrei I. Chapoval

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The aim of this work was to test for cure and immunity in a micrometastatic tumor model using in vivo T cell activation with staphylococcal enterotoxin B (SEB) and retargeting with antitumorxanti-CD3 F(ab')2 bispecific antibodies (bsAb). All studies were performed in C3H/HeN mice using syngeneic tumor cell lines. For survival studies, mice were injected intravenously on day 0 with CL62 (a p97-transfected clone of the K1735 murine melanoma tumor). Day-3 treatments included saline (control), SEB (50 γg intraperitoneal) with or without bsAb (5 μg i.v.). Cured mice, surviving beyond 60 days, were rechallenged with subcutaneous CL62, K1735, or a nonmelanoma control, AG104. SEB activation studies were performed with pulmonary tumor-infiltrating lymphocytes isolated from 10-day established CL62 tumors. Maximal tumor-infiltrating lymphocyte cytotoxicity was demonstrated 24 h following SEB injection, therefore bsAb treatments were administered 24 h after SEB. When survival was examined at 60 days, there were significantly more survivors in the group receiving SEB plus bsAb (70%) compared to the group receiving SEB alone (30%), and the controls (0%) (P=0.02 and P<0.01, respectively). Mice cured of CL62 using SEB alone or with bsAb demonstrated equal immunity to CL62, however, mice treated with SEB plus bsAb were more often immune to the p97- parental cell line, K1735(P=0.001). Ag104 consistently grew in all mice. Results of these studies demonstrate that SEB plus bsAb can be effective, not only in curing tumors but also in providing protective immunity against targeted and nontargeted tumor antigens.

Original languageEnglish (US)
Pages (from-to)180-183
Number of pages4
JournalCancer Immunology Immunotherapy
Volume45
Issue number3-4
DOIs
StatePublished - 1997

Fingerprint

Bispecific Antibodies
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Immunity
Neoplasms
staphylococcal enterotoxin B
Inbred C3H Mouse
Neoplasm Antigens
Tumor Cell Line
Melanoma
Clone Cells

Keywords

  • Bispecific antibodies
  • Micrometastatic
  • T cell activation
  • Tumor immunity

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

T cell activation and retargeting using staphylococcal enterotoxin B and bispecific antibody : An effective in vivo antitumor strategy. / Porter, Lewis E.; Nelson, Heidi; Gecim, I. Ethem; Rice, David C.; Thibault, Claude; Chapoval, Andrei I.

In: Cancer Immunology Immunotherapy, Vol. 45, No. 3-4, 1997, p. 180-183.

Research output: Contribution to journalArticle

Porter, Lewis E. ; Nelson, Heidi ; Gecim, I. Ethem ; Rice, David C. ; Thibault, Claude ; Chapoval, Andrei I. / T cell activation and retargeting using staphylococcal enterotoxin B and bispecific antibody : An effective in vivo antitumor strategy. In: Cancer Immunology Immunotherapy. 1997 ; Vol. 45, No. 3-4. pp. 180-183.
@article{d6236e2bc30a41eabc78d8646bd076fd,
title = "T cell activation and retargeting using staphylococcal enterotoxin B and bispecific antibody: An effective in vivo antitumor strategy",
abstract = "The aim of this work was to test for cure and immunity in a micrometastatic tumor model using in vivo T cell activation with staphylococcal enterotoxin B (SEB) and retargeting with antitumorxanti-CD3 F(ab')2 bispecific antibodies (bsAb). All studies were performed in C3H/HeN mice using syngeneic tumor cell lines. For survival studies, mice were injected intravenously on day 0 with CL62 (a p97-transfected clone of the K1735 murine melanoma tumor). Day-3 treatments included saline (control), SEB (50 γg intraperitoneal) with or without bsAb (5 μg i.v.). Cured mice, surviving beyond 60 days, were rechallenged with subcutaneous CL62, K1735, or a nonmelanoma control, AG104. SEB activation studies were performed with pulmonary tumor-infiltrating lymphocytes isolated from 10-day established CL62 tumors. Maximal tumor-infiltrating lymphocyte cytotoxicity was demonstrated 24 h following SEB injection, therefore bsAb treatments were administered 24 h after SEB. When survival was examined at 60 days, there were significantly more survivors in the group receiving SEB plus bsAb (70{\%}) compared to the group receiving SEB alone (30{\%}), and the controls (0{\%}) (P=0.02 and P<0.01, respectively). Mice cured of CL62 using SEB alone or with bsAb demonstrated equal immunity to CL62, however, mice treated with SEB plus bsAb were more often immune to the p97- parental cell line, K1735(P=0.001). Ag104 consistently grew in all mice. Results of these studies demonstrate that SEB plus bsAb can be effective, not only in curing tumors but also in providing protective immunity against targeted and nontargeted tumor antigens.",
keywords = "Bispecific antibodies, Micrometastatic, T cell activation, Tumor immunity",
author = "Porter, {Lewis E.} and Heidi Nelson and Gecim, {I. Ethem} and Rice, {David C.} and Claude Thibault and Chapoval, {Andrei I.}",
year = "1997",
doi = "10.1007/s002620050427",
language = "English (US)",
volume = "45",
pages = "180--183",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "3-4",

}

TY - JOUR

T1 - T cell activation and retargeting using staphylococcal enterotoxin B and bispecific antibody

T2 - An effective in vivo antitumor strategy

AU - Porter, Lewis E.

AU - Nelson, Heidi

AU - Gecim, I. Ethem

AU - Rice, David C.

AU - Thibault, Claude

AU - Chapoval, Andrei I.

PY - 1997

Y1 - 1997

N2 - The aim of this work was to test for cure and immunity in a micrometastatic tumor model using in vivo T cell activation with staphylococcal enterotoxin B (SEB) and retargeting with antitumorxanti-CD3 F(ab')2 bispecific antibodies (bsAb). All studies were performed in C3H/HeN mice using syngeneic tumor cell lines. For survival studies, mice were injected intravenously on day 0 with CL62 (a p97-transfected clone of the K1735 murine melanoma tumor). Day-3 treatments included saline (control), SEB (50 γg intraperitoneal) with or without bsAb (5 μg i.v.). Cured mice, surviving beyond 60 days, were rechallenged with subcutaneous CL62, K1735, or a nonmelanoma control, AG104. SEB activation studies were performed with pulmonary tumor-infiltrating lymphocytes isolated from 10-day established CL62 tumors. Maximal tumor-infiltrating lymphocyte cytotoxicity was demonstrated 24 h following SEB injection, therefore bsAb treatments were administered 24 h after SEB. When survival was examined at 60 days, there were significantly more survivors in the group receiving SEB plus bsAb (70%) compared to the group receiving SEB alone (30%), and the controls (0%) (P=0.02 and P<0.01, respectively). Mice cured of CL62 using SEB alone or with bsAb demonstrated equal immunity to CL62, however, mice treated with SEB plus bsAb were more often immune to the p97- parental cell line, K1735(P=0.001). Ag104 consistently grew in all mice. Results of these studies demonstrate that SEB plus bsAb can be effective, not only in curing tumors but also in providing protective immunity against targeted and nontargeted tumor antigens.

AB - The aim of this work was to test for cure and immunity in a micrometastatic tumor model using in vivo T cell activation with staphylococcal enterotoxin B (SEB) and retargeting with antitumorxanti-CD3 F(ab')2 bispecific antibodies (bsAb). All studies were performed in C3H/HeN mice using syngeneic tumor cell lines. For survival studies, mice were injected intravenously on day 0 with CL62 (a p97-transfected clone of the K1735 murine melanoma tumor). Day-3 treatments included saline (control), SEB (50 γg intraperitoneal) with or without bsAb (5 μg i.v.). Cured mice, surviving beyond 60 days, were rechallenged with subcutaneous CL62, K1735, or a nonmelanoma control, AG104. SEB activation studies were performed with pulmonary tumor-infiltrating lymphocytes isolated from 10-day established CL62 tumors. Maximal tumor-infiltrating lymphocyte cytotoxicity was demonstrated 24 h following SEB injection, therefore bsAb treatments were administered 24 h after SEB. When survival was examined at 60 days, there were significantly more survivors in the group receiving SEB plus bsAb (70%) compared to the group receiving SEB alone (30%), and the controls (0%) (P=0.02 and P<0.01, respectively). Mice cured of CL62 using SEB alone or with bsAb demonstrated equal immunity to CL62, however, mice treated with SEB plus bsAb were more often immune to the p97- parental cell line, K1735(P=0.001). Ag104 consistently grew in all mice. Results of these studies demonstrate that SEB plus bsAb can be effective, not only in curing tumors but also in providing protective immunity against targeted and nontargeted tumor antigens.

KW - Bispecific antibodies

KW - Micrometastatic

KW - T cell activation

KW - Tumor immunity

UR - http://www.scopus.com/inward/record.url?scp=0030727184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030727184&partnerID=8YFLogxK

U2 - 10.1007/s002620050427

DO - 10.1007/s002620050427

M3 - Article

C2 - 9435868

AN - SCOPUS:0030727184

VL - 45

SP - 180

EP - 183

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 3-4

ER -