Depletion of activated Vbeta8+ T cells disrupts bispecific antibody directed antitumor immunity.

Abstract

INTRODUCTION:

Activation of Vbeta8+ T cells with superantigen staphylococcal enterotoxin B (SEB) and use of an antitumor, anti-CD3 bispecific antibody (BsAb) leads to tumor protective immunity. We hypothesize that Vbeta8+ T-cell activation in combination with BsAb is crucial for tumor protective immunity in this model.

METHODS:

Adolescent C3H/HeN mice were intravenously injected with syngeneic CL62 melanoma to establish pulmonary metastasis. Three days after establishing pulmonary metastasis, predominantly Vbeta8+ T cells are activated with 50 mug of intraperitoneal superantigen SEB. T cells were depleted at different time points in relation to SEB administration to assess the effect on protective immunity against a second tumor challenge.

RESULTS:

Protective immunity is significantly (P < 0.008) decreased when Vbeta8+ depletion occurs 6 h after SEB injection, as growth of rechallenged CL62 melanoma occurred in 43%. Protective immunity is present at all other time points when mice survive Vbeta8+ T-cell depletion. Survival of animals treated with SEB/BsAb (82%) is significantly better (P < 0.002) than with SEB alone (60%) or nontreated control (0%). Survival when Vbeta8+ T-cell depletion occurred at 6 h and 48 h post-SEB is 72% and 77%, respectfully, and is statistically indistinguishable (P < 0.232 and P < 0.602). If T-cell depletion was conducted before SEB administration, however, the combination of SEB and BsAb did not result in significant protective immunity. T-cell depletion before the use of SEB alone, without BsAb, failed to result in significant protective immunity.

CONCLUSIONS:

Depletion of Vbeta8+ T cells 6 h after activation disrupts the development of protective immunity.

• Authors: Elizabeth J McConnell, Elisabeth C McLemore, Robert Talac, Lokesh Joshi, Heidi Nelson
• Journal: The Journal of surgical research (J Surg Res) Vol. 122 Issue 1 Pg. 103-12 (Nov 2004) ISSN: 0022-4804 [Print] United States
• PMID: 15522322 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bispecific
• CD3 Complex
• Cytokines
• Enterotoxins
• Interleukin-2
• Superantigens
• enterotoxin B, staphylococcal
• Interferon-gamma

Topics

• Animals
• Antibodies, Bispecific (immunology)
• CD3 Complex (immunology)
• Cell Line, Tumor
• Cytokines (deficiency)
• Enterotoxins (pharmacology)
• Immunity
• Immunologic Memory
• Interferon-gamma (blood)
• Interleukin-2 (blood)
• Lung Neoplasms (immunology, secondary)
• Lymphocyte Activation
• Lymphocyte Count
• Melanoma (immunology, secondary)
• Mice
• Mice, Inbred C3H
• Neoplasm Transplantation
• Superantigens (pharmacology)
• Survival Analysis
• T-Lymphocytes (drug effects, immunology, metabolism, pathology)
• T-Lymphocytes, Cytotoxic (immunology)
• Time Factors