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Immunotherapy Using Chimeric Antigen Receptor Macrophage

  • Author(s): Huang, Peng Fei
  • Advisor(s): Xu, Yang
  • et al.
Abstract

Chimeric antigen receptor (CAR) T cell immunotherapy has become one of the most prominent and leading cancer therapies due to its remarkable success in targeting hematological malignancies. Unfortunately, CAR-T cell immunotherapy has not had the same amount of success in solid tumors due to the challenging tumor’s immunosuppressive microenvironment. Therefore, we hypothesize the use of macrophages as a vessel for CAR immunotherapy due to their associate with tumors as TAMs and also the tumors ability to secrete various chemokines that can attract myeloid cells to the tumor site. THP-1 a monocytic cell line that represents a monocyte/macrophage model was transduced with an anti-CD19 scFv CAR construct. K562 a leukemia cell line that represents hematological malignancies and H460 a lung cancer cell line that represents solid tumors were transduced to overexpress the surface marker CD19. THP-1 clones expressing the anti-CD19 CAR construct were cocultured with the two tumor cell lines, which demonstrated the ability of the THP-1 CARs to specifically targeted and lysis the tumor cells that overexpressed the CD19 surface marker. Upon CAR activation, THP-1 cells were polarized towards the M1 classical activated phenotype due to the increase in expression of TNF-α, IL-1β, IL-6, IL-12β, CXCl10, HLA-DR, and CD86. Additionally, THP-1 cells did not show any change in the M2 alternative activated markers of IL10, TFGβ, CCL18, CCL22, CD206, and CD204 to suggest polarization towards the M2 phenotype. As a result, this study validates the proof of concept that macrophages could potentially be a vessel for CAR immunotherapy.

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