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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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Polymer Micropatches as B-Cell Engagers.

Supriya Prakash1,2, Ninad Kumbhojkar1,2, Alexander P Gottlieb1,2

  • 1Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, Massachusetts 02134, United States.

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|May 21, 2024
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Micropatches as Cell Engagers (MACE) enhance B cells for adoptive cell therapy. MACE-bound B cells show improved antigen presentation and delay tumor growth in mice, unlocking B cell potential.

Keywords:
APCB cellsB-cell activationMACEcancer vaccinecellular vaccine

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Area of Science:

  • Immunology
  • Cell Therapy
  • Biotechnology

Background:

  • B cells are underutilized in adoptive cell therapy despite their antigen-presenting capabilities.
  • Current methods for B cell activation in vivo are limited by difficulties in achieving sufficient concentrations of stimulating biologics.
  • Dendritic cells (DCs) have shown limited efficacy as antigen-presenting cells (APCs) in clinical settings.

Purpose of the Study:

  • To investigate the potential of Micropatches as Cell Engagers (MACE) to enhance B cell function for adoptive cell therapy.
  • To evaluate MACE-mediated B cell activation, antigen presentation, and in vivo therapeutic efficacy.
  • To explore B cells as a viable alternative to DCs for cellular immunotherapy.

Main Methods:

  • MACE, polymeric microparticles functionalized with anti-CD40 and anti-IgM, were used to engage B cells.
  • B cell activation, costimulatory molecule expression, viability, and antigen presentation to T cells were assessed in vitro.
  • MACE-bound B cells were adoptively transferred into a murine tumor model to evaluate in vivo homing and anti-tumor activity.

Main Results:

  • MACE stimulation enhanced B cell display of costimulatory molecules, increased viability, and improved antigen presentation in vitro.
  • MACE-bound B cells exhibited enhanced T cell chemokine secretion and synergized with soluble IL-4 and anti-CD40.
  • Adoptively transferred MACE-bound B cells successfully homed to lymphoid organs and significantly delayed tumor progression in a murine model.

Conclusions:

  • MACE technology effectively enhances B cell activation and function, positioning them as potent APCs for adoptive cell therapy.
  • MACE-bound B cells demonstrate promising in vivo homing and anti-tumor efficacy, overcoming limitations of traditional B cell therapies.
  • This approach offers a novel strategy to harness B cells for cancer immunotherapy and other therapeutic applications.