Alpha Particles Induce Autophagy in Multiple Myeloma Cells.

Area of Science:

• Radioimmunotherapy (RIT)
• Nuclear medicine
• Oncology

Background:

• Radioimmunotherapy (RIT) utilizes radionuclides to induce cancer cell death via direct and bystander effects.
• Alpha-particle RIT (α-RIT) is being developed for multiple myeloma (MM).
• The cell death mechanisms induced by Bismuth-213 (213Bi) α-irradiation in MM require further investigation.

Purpose of the Study:

• To investigate the radiobiology of 213Bi α-irradiation in multiple myeloma (MM) cells.
• To elucidate the cell death mechanisms, including apoptosis and autophagy, induced by 213Bi.
• To assess the impact of 213Bi irradiation on MM cell immunogenicity and dendritic cell activation.

Main Methods:

• Murine (5T33) and human (LP-1) MM cell lines were exposed to 213Bi.
• Assessed proliferation, DNA double-strand breaks, cell cycle, cell death (apoptosis, necrosis), and autophagy.
• Investigated dendritic cell (DC) activation using cocultures with irradiated MM cells or their media.

Main Results:

• 213Bi induced DNA double-strand breaks, cell cycle arrest, and autophagy in MM cells.
• Apoptosis levels were low, with necrosis being the predominant cell death mode.
• Autophagy inhibition partially reversed proliferation inhibition in LP-1 cells.
• Irradiated LP-1 cells activated DCs via soluble factors, without increasing danger-associated molecular patterns.

Conclusions:

• 213Bi α-irradiation induces predominantly necrosis and autophagy in MM cells, with limited apoptosis.
• Autophagy plays a role in 213Bi-mediated proliferation inhibition.
• Irradiated MM cells can enhance DC activation, indicating potential immunomodulatory effects relevant to α-RIT.