Interrogating the Safety and Efficacy of a Novel STEAP1 Chimeric Antigen Receptor T-Cell Therapy in Prostate Cancer

Abstract

In this reporting period, we completed studies profiling the response of the prostate cancer tumor immune microenvironment to collagen binding domain (CBD)-IL-12 fusion cytokine therapy in conjunction with STEAP1 CAR T cell therapy. CBD-IL-12 induced a significant increase in mature antigen-presenting macrophages with M1 polarization and an expansion of type 1 conventional dendritic cells. These data indicate that CBD-IL-12 can help revert the hostile immunosuppressive tumor microenvironment to a pro-inflammatory state that enhances the activity of adoptively transferred STEAP1 CAR T cells. Further, we previously showed that CBD-IL-12 can restore a deficit in antigen processing and presentation associated with STEAP1antigen loss arising from STEAP1 CAR T cell therapy. These findings taken together provide a strong rationale for combination therapy with CBD-IL-12 and STEAP1 CAR T cell therapy in advanced prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2023
Accession Number
AD1213944

Entities

People

  • Bethany Stackhouse
  • John K Lee
  • Jun Ishihara
  • Koichi Sasaki
  • Li-ting Wu
  • Patrick Paddison
  • Vipul Bhatia

Organizations

  • Fred Hutchinson Cancer Center

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Biological Factors
  • Blood
  • Body Weight
  • Cancer
  • Cardiovascular System
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Gene Expression
  • Gene Therapy
  • Lymphatic System
  • Lymphocytes
  • Medical Personnel
  • Mononuclear Phagocyte System
  • Neoplasms
  • Oncology
  • Phagocytes
  • Prostate Cancer
  • Proteins
  • Therapy

Fields of Study

  • Medicine

Readers

  • Data Mining and Knowledge Discovery.
  • Immunology and Pathology
  • Molecular Biology and Genetics