Antitumor x anti-CD3 bifunctional antibodies redirect T-cells activated in vivo with staphylococcal enterotoxin B to neutralize pulmonary metastases

Christophe Penna, Phillip A. Dean, Heidi Nelson

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

T-cell antitumor activities are limited by the requirement of two specific major histocompatibility complex restricted steps, T-helper cell activation and cytotoxic T-lymphocyte targeting. The aim of this study was to investigate whether bypassing these major histocompatibility complex restricted steps using nonspecific in vivo activation of T-cells with staphylococcal enterotoxin-B (SE-B) and retargeting with antitumor x anti- CD3 bifunctional antibody (BFA) could provide an effective antitumor response. C3H/HeN mice were injected i.v. with CL-62 melanoma cells, which express the human melanoma antigen p97, and were treated 10 min later with SE-B and/or anti-CD3 (500A2) x anti-p97 (96.5) BFA. Pulmonary metastases were counted 14 days following injections. SE-B alone induced a dose-dependant activation of T-cells as measured by increased interleukin-2 receptor expression and enhanced proliferative responses. SE-B doses greater than 10 μg significantly reduced the number of pulmonary metastases versus control (P < 0.01). Combined treatment with SE-B (50 μg) and BFA (5 to 50 μg) significantly decreased pulmonary metastases compared to treatment with SE-B alone (P < 0.05). Similar reductions in metastases were observed with the F(ab')2 BFA but not with the unconjugated antitumor component of the BFA. Combined treatments with SE-B plus BFA accomplished better tumor neutralization than adoptively transferred in vitro activated splenocytes (4 x 107) retargeted with BFA (5-100 μg; P < 0.05). These studies demonstrate that T-cells can be activated in vivo by SE-B and retargeted with small doses of BFA. In this immunocompetent syngeneic pulmonary metastasis model, SE-B plus BFA provided a dramatic antitumor response.

Original languageEnglish (US)
Pages (from-to)2738-2743
Number of pages6
JournalCancer Research
Volume54
Issue number10
StatePublished - May 15 1994

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Bispecific Antibodies
Neoplasm Metastasis
T-Lymphocytes
Lung
Major Histocompatibility Complex
Melanoma-Specific Antigens
staphylococcal enterotoxin B
Inbred C3H Mouse
Interleukin-2 Receptors
Cytotoxic T-Lymphocytes
Helper-Inducer T-Lymphocytes
Melanoma
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Antitumor x anti-CD3 bifunctional antibodies redirect T-cells activated in vivo with staphylococcal enterotoxin B to neutralize pulmonary metastases. / Penna, Christophe; Dean, Phillip A.; Nelson, Heidi.

In: Cancer Research, Vol. 54, No. 10, 15.05.1994, p. 2738-2743.

Research output: Contribution to journalArticle

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