A Proteomics Outlook on the Molecular Effectors of CAR-T Cell Therapy in Cancer Management

Author(s)

Teibo, John Oluwafemi ; Picanco-Castro, Virginia ; de Souza, Lucas Eduardo Botelho ; Faca, Vitor Marcel

• Document type: Journal article
• Source: JOURNAL OF PROTEOME RESEARCH; v. N/A, p. 13-pg., 2025-03-06.

Abstract

In the field of cell and immunotherapy, chimeric antigen receptor T-cell (CAR-T cell) therapy is the state-of-the-art therapy. It utilizes genetically engineered T cells expressing receptors against specific tumor cell targets such as CD-19 to induce cytotoxicity in and kill malignant cells. CAR-T cell therapy has demonstrated tremendous success in hematological cancers and promising results in solid tumors. However, CAR-T cell therapy has some limitations, such as causing cytokine release syndrome and neurologic abnormalities, leading to loss of target, and, most importantly, its high cost. Profiling the molecular mechanisms of CAR-T has provided important contributions to decomplexing biology and understanding more refined signaling and function of the cell therapy. Proteomics can elucidate alterations in effector molecules. We searched for CAR-T cell therapy-related molecular effectors in databases such as PUBMED and SCOPUS. We found based on our analysis, certain proteins (CD28, IFNG, IL-2, IL-5, CCL3, granzyme B, LCK, TNF-alpha, CD3E, CD80, B-Raf, ITK, and JAK2) that might be key effectors in the refinement of CAR-T cell therapy effectiveness. This review presents an overview of the key findings from proteomics studies related to CAR-T cell therapy, highlighting the critical proteins and signaling pathways involved in the therapy efficacy. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/13463-2 - Proteomic and phosphoproteomic analysis of molecular mechanisms and signaling for Anti CD-19 CAR-T cell therapy in Leukemia and Lymphoma
• Grantee: John Oluwafemi Teibo
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 23/07866-5 - Establishing strategies to study the spatial complexity of the tumor proteome
• Grantee: Vitor Marcel Faça
• Support Opportunities: Regular Research Grants