TY - JOUR
T1 - Depletion of activated Vβ8+ T cells disrupts bispecific antibody directed antitumor immunity
AU - McConnell, Elizabeth J.
AU - McLemore, Elisabeth C.
AU - Talac, Robert
AU - Joshi, Lokesh
AU - Nelson, Heidi
N1 - Funding Information:
Supported by an intramural grant from the Department of Colon and Rectal Surgery of the Mayo Foundation.
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
KW - Vβ8+ T cell
KW - bispecific antibody
KW - immunotherapy
KW - protective immunity
KW - staphylococcal enterotoxin B
UR - http://www.scopus.com/inward/record.url?scp=7444231527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7444231527&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2004.06.017
DO - 10.1016/j.jss.2004.06.017
M3 - Article
C2 - 15522322
AN - SCOPUS:7444231527
SN - 0022-4804
VL - 122
SP - 103
EP - 112
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -