Multipeptide stimulated PBMCs generate T_EM/T_CM for adoptive cell therapy in multiple myeloma

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• Multiple Myeloma (MM) is characterized by therapeutic resistance and disease relapse.
• Immunotherapy, including adoptive cell transfer (ACT), offers potential for durable responses in MM.
• Generating patient-specific T cells is crucial for effective ACT strategies.

Purpose of the Study:

• To evaluate the feasibility of generating antigen-specific T cells from MM patients for ACT.
• To identify effective peptide antigens and cocktails for T cell activation in MM.
• To assess the functional and metabolic capacity of T cells generated from MM patients.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) from MM patients and healthy donors (HDs) were used.
• PBMCs were exposed to custom-designed peptides from overexpressed antigens, including cancer testis antigens (CTAs).
• Ag-specific CD4+ and CD8+ T cell responses, including cytokine production and metabolic switching, were analyzed.

Main Results:

• Peptide cocktails reproducibly induced antigen-specific CD4+ and CD8+ T cell responses in both MM patients and HDs.
• Generated T cells exhibited effector and central memory phenotypes, producing IFN-γ, granzyme B, and perforin.
• Immune cells from MM patients demonstrated metabolic plasticity supporting effector and memory T cell generation.

Conclusions:

• Identified peptide cocktails effectively induce functional, metabolically active T cells from MM patients.
• These findings support the feasibility of ACT for MM and warrant further investigation in Phase I clinical trials.
• This approach holds potential for overcoming therapeutic resistance in multiple myeloma.