RGD Reference Report - Abrogating Cbl-b in effector CD8(+) T cells improves the efficacy of adoptive therapy of leukemia in mice. - Rat Genome Database

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Abrogating Cbl-b in effector CD8(+) T cells improves the efficacy of adoptive therapy of leukemia in mice.

Authors: Stromnes, IM  Blattman, JN  Tan, X  Jeevanjee, S  Gu, H  Greenberg, PD 
Citation: Stromnes IM, etal., J Clin Invest. 2010 Oct;120(10):3722-34. doi: 10.1172/JCI41991. Epub 2010 Sep 20.
RGD ID: 11038805
Pubmed: (View Article at PubMed) PMID:20890046
DOI: Full-text: DOI:10.1172/JCI41991

The clinical use of adoptive immunotherapy with tumor-reactive T cells to treat established cancers is limited in part by the poor in vivo survival and function of the transferred T cells. Although administration of exogenous cytokines such as IL-2 can promote T cell survival, such strategies have many nonspecific activities and are often associated with toxicity. We show here that abrogating expression of Casitas B-lineage lymphoma b (Cbl-b), a negative regulator of lymphocyte activation, in tumor-reactive CD8(+) T cells expanded ex vivo increased the efficacy of adoptive immunotherapy of disseminated leukemia in mice. Mechanistically, Cbl-b abrogation bypassed the requirement for exogenous IL-2 administration for tumor eradication in vivo. In addition, CD8(+) T cells lacking Cbl-b demonstrated a lower threshold for activation, better survival following target recognition and stimulation, and enhanced proliferative responses as a result of both IL-2-dependent and -independent pathways. Importantly, siRNA knockdown of Cbl-b in human CD8(+)CD28- effector T cell clones similarly restored IL-2 production and proliferation following target recognition independent of exogenous IL-2, enhanced IFN-gamma production, and increased target avidity. Thus, abrogating Cbl-b expression in effector T cells may improve the efficacy of adoptive therapy of some human malignancies.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Cbl  (Cbl proto-oncogene)

Genes (Mus musculus)
Cbl  (Casitas B-lineage lymphoma)

Genes (Homo sapiens)
CBL  (Cbl proto-oncogene)


Additional Information