Immuno-PET Monitoring of Lymphocytes Using the CD8-Specific Antibody REGN5054

Area of Science:

• Immunology
• Oncology
• Radiochemistry

Background:

• Assessing the tumor immune microenvironment is crucial for understanding cancer immunotherapy effectiveness.
• Traditional biopsy methods for tumor immune microenvironment assessment face limitations such as sampling error and restricted temporal analysis.
• Immuno-positron emission tomography (PET) offers a potential solution for non-invasive monitoring of the tumor microenvironment.

Purpose of the Study:

• To develop and validate a novel immuno-PET agent, 89Zr-DFO-REGN5054, for assessing CD8+ tumor-infiltrating lymphocytes (TILs).
• To evaluate the safety and efficacy of 89Zr-DFO-REGN5054 in preclinical models.
• To support the clinical investigation of 89Zr-DFO-REGN5054 for monitoring T-cell responses during cancer immunotherapy.

Main Methods:

• Development of a fully human CD8A-specific antibody conjugate, 89Zr-DFO-REGN5054.
• In vitro assays (T-cell activation, proliferation, cytokine production) and in vivo studies (viral clearance, receptor occupancy) to assess REGN5054's impact on T-cell activity.
• Preclinical immuno-PET studies in CD8-genetically humanized mice and toxicology studies in cynomolgus monkeys.

Main Results:

• REGN5054 demonstrated minimal impact on T-cell activity.
• 89Zr-DFO-REGN5054 specifically detected CD8+ T cells in lymphoid tissues and discerned therapy-induced changes in CD8+ TILs in preclinical models.
• Toxicology studies showed no overt toxicity in monkeys, and imaging confirmed dose-dependent clearance and specific targeting.

Conclusions:

• 89Zr-DFO-REGN5054 is a promising immuno-PET agent for non-invasively assessing CD8+ TILs.
• This agent can overcome limitations associated with traditional biopsy methods.
• The findings support the clinical use of 89Zr-DFO-REGN5054 to monitor T-cell responses in cancer immunotherapy patients.