CD19 Chimeric Antigen Receptor (CAR) modified cytokine killer cells compared to classical CD19 CAR-T: advantages and disadvantages

• DOI: 10.3889/seejim.2025.6123
• Publication Date: 2025-03-31T10:12:15Z
• Authors: Olha Karaman; Madeline Kim; Gina Scurti; Jan Aleksander Kr...; Oliwia Bochnacka; Suzanne Quinn; Vita Pasukoniene; Michael I. Nishimura

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy and unique long-term outcomes in treating relapsed/refractory hematological malignancies both pediatric adult patients. However, a subset of patients remains unresponsive, with disease progression continuing despite treatment. Moreover, CAR-T shown limited success solid tumors. Accumulating evidence on the role various lymphocyte subpopulations antitumor immunity suggests that cytokine-induced killer (CIKs) cells represent promising alternative for adoptive cell therapy. A key advantage CIKs is their low toxicity presence unrestricted MHC cytotoxicity against malignancies. In our study, we hypothesize modifying CARs would enhance compared to unmodified CIKs. Using retroviral vector containing CD34 or CD14 marker gene, successfully generated CD19 CAR-expressing populations, including classically activated T lymphocytes We then functional properties by analyzing based markers such as CD3, CD4, CD8, CD56, CD62L, CD45RA, well ability specifically recognize CD19-positive targets. Additionally, assessed cytokine production, IFN-γ (via ELISA intracellular staining), IL-2, TNF-α, IL-10 staining). Our findings indicate can be efficiently modified using while maintaining activity. CAR-CIK populations contained higher numbers NKT (CD3⁺CD56⁺) CD3⁺CD8⁺ cells. proportion naïve-like (CD62L⁺CD45RA⁺) effector memory RA⁺ (CD62L⁻CD45RA⁺) remained similar CAR-modified populations. CAR-CIKs exhibited slightly increased produce TNF-α response CD19⁺ tumor Despite that, questions remain regarding functionality an immunosuppressive microenvironment, particularly high levels TGF-β, IL-10, PD-L1, which may inhibit activity lead exhaustion. future research will focus overcoming these challenges therapeutic potential CAR-CIKs.