Authors: Sansana Sawasdikosol Renyuan Zha Boyu Yang Steven Burakoff
Publish Date: 2012/04/04
Volume: 54, Issue: 1-3, Pages: 262-265
Abstract
Identifying the appropriate drug targets for the development of a novel antitumor immunotherapy is one of the most risky steps in the drug development cycle We have identified a hematopoietic cellrestricted serine/threonine kinase hematopoietic progenitor kinase 1 HPK1 as a possible target for therapeutic intervention Targeted disruption of HPK1 alleles confers T cells with an elevated Th1 cytokine production in response to TCR engagement HPK1 −/− T cells proliferate more rapidly than the haplotypematched wildtype counterpart and are resistant to prostaglandin E2 PGE2mediated suppression Most strikingly mice that received adoptive transfer of HPK1 −/− T cells became resistant to lung tumor growth Also the loss of HPK1 from dendritic cells DCs endows them with superior antigen presentation ability enabling HPK1 −/− DCs to elicit a more potent antitumor immune response when used as cancer vaccine It is probable that blocking the HPK1 kinase activity with a small molecule inhibitor may activate the superior antitumor activity of both cell types resulting in a synergistic amplification of antitumor potential Given that HPK1 is not expressed in any major organs it is less likely that an inhibitor of HPK1 kinase activity would cause any serious side effects
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