Depletion of activated Vβ8+ T cells disrupts bispecific antibody directed antitumor immunity

Elizabeth J. McConnell, Elisabeth C. McLemore, Robert Talac, Lokesh Joshi, Heidi Nelson

Research output: Contribution to journalArticle

Abstract

Activation of Vβ8+ 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 Vβ8+ T-cell activation in combination with BsAb is crucial for tumor protective immunity in this model. Adolescent C3H/HeN mice were intravenously injected with syngeneic CL62 melanoma to establish pulmonary metastasis. Three days after establishing pulmonary metastasis, predominantly Vβ8+ T cells are activated with 50 μg 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. Protective immunity is significantly (P < 0.008) decreased when Vβ8+ 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 Vβ8+ 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 Vβ8+ 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. Depletion of Vβ8+ T cells 6 h after activation disrupts the development of protective immunity.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalJournal of Surgical Research
Volume122
Issue number1
DOIs
StatePublished - Nov 1 2004

Keywords

  • Vβ8+ T cell
  • bispecific antibody
  • immunotherapy
  • protective immunity
  • staphylococcal enterotoxin B

ASJC Scopus subject areas

  • Surgery

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