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Development and Functional Characterization of a Versatile Radio-/Immunotheranostic Tool for Prostate Cancer

Claudia Arndt1,2, Ralf Bergmann1,3, Franziska Striese1

  • 1Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, D-01328 Dresden, Germany.

Cancers
|April 23, 2022
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Summary

A novel antibody derivative targeting prostate stem cell antigen (PSCA) enables prostate cancer (PCa) diagnosis and therapy. This immunotheranostic compound facilitates imaging, targeted alpha therapy, and CAR T cell immunotherapy for improved PCa treatment.

Keywords:
(18)F-JK-PSMA-7Ac-225CAR T cellCu-64IgG4PSCAPSMAprostate cancertheranostics

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Area of Science:

  • Oncology
  • Immunotherapy
  • Radiochemistry

Background:

  • Prostate stem cell antigen (PSCA) is overexpressed on prostate cancer (PCa) cells, making it a promising target for diagnosis and therapy.
  • Current therapeutic strategies for PCa require novel approaches for effective treatment and monitoring.

Purpose of the Study:

  • To develop and characterize a novel IgG4-based anti-PSCA antibody derivative (anti-PSCA IgG4-TM) for multimodal immunotheranostic applications.
  • To evaluate the efficacy of anti-PSCA IgG4-TM in preclinical models for immunotherapy, diagnostic imaging, and targeted alpha therapy.

Main Methods:

  • Development of an anti-PSCA IgG4 antibody conjugated with DOTAGA chelator.
  • Functional characterization of the anti-PSCA IgG4-TM for UniCAR T cell-based immunotherapy.
  • Radiolabeling with Copper-64 (64Cu2+) for positron emission tomography (PET) imaging.
  • Radiolabeling with Actinium-225 (225Ac3+) for targeted alpha therapy in a PCa mouse model.

Main Results:

  • The anti-PSCA IgG4-TM effectively mediated lysis of PSCA-positive tumor cells in vitro and in vivo via UniCAR T cell cross-linkage.
  • 64Cu-labeled anti-PSCA IgG4-TM enabled high-contrast PET imaging with specific tumor accumulation in a PCa mouse model.
  • 225Ac-labeled anti-PSCA IgG4-TM demonstrated significant tumor growth control after a single injection in experimental mice.

Conclusions:

  • The novel anti-PSCA IgG4-TM is a versatile immunotheranostic agent for prostate cancer.
  • This compound supports diagnostic imaging, targeted alpha therapy, and CAR T cell immunotherapy.
  • The anti-PSCA IgG4-TM represents a promising new class of radio-/immunotheranostics for comprehensive PCa management.