Identifying the appropriate drug targets for the development of a novel anti-tumor immunotherapy is one of the most risky steps in the drug development cycle. We have identified a hematopoietic cell-restricted 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 haplotype-matched wild-type counterpart and are resistant to prostaglandin E2 (PGE 2)-mediated 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 anti-tumor 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 anti-tumor activity of both cell types, resulting in a synergistic amplification of anti-tumor 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.

Original languageEnglish
Pages (from-to)262-265
Number of pages4
JournalImmunologic Research
Issue number1-3
StatePublished - Dec 2012


  • Anti-tumor immunotherapy
  • Cancer vaccine
  • Dendritic cells
  • Drug target
  • Kinase
  • Kinase inhibitor
  • Prostaglandin E2
  • T cells


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