Abstract：
B cells, despite their several unique functionalities, remain largely untapped for use as an adoptive cell therapy and are limited to in vitro use for antibody production. B cells can be easily sourced, they possess excellent lymphoid-homing capabilities, and they can act as antigen-presenting cells (APCs), offering an alternative to dendritic cells (DCs), which have shown limited efficacy in the clinical setting. Soluble factors such as IL-4 and anti-CD40 antibody can enhance the activation, survival, and antigen-presenting capabilities of B cells; however, it is difficult to attain sufficiently high concentrations of these biologics to stimulate B cells in vivo. Micropatches as Cell Engagers (MACE) are polymeric microparticles, surface functionalized with anti-CD40 and anti-IgM, which can attach to B cells and simultaneously engage multiple B-cell receptors (BCR) and CD40 receptors. Stimulation of these receptors through MACE, unlike free antibodies, enhanced the display of costimulatory molecules on the B-cell surface, increased B-cell viability, and improved antigen presentation by B cells to T cells in vitro. B-cell activation by MACE further synergized with soluble IL-4 and anti-CD40. MACE also elicited T-cell chemokine secretion by B cells. Upon intravenous adoptive transfer, MACE-bound B cells homed to the spleen and lymph nodes, key sites for antigen presentation to T cells. Adoptive transfer of MACE-B cells pulsed with the CD4+ and CD8+ epitopes of ovalbumin significantly delayed tumor progression in a murine subcutaneous EG7-OVA tumor model, demonstrating the functional benefit conferred to B cells by MACE.
摘要：
B细胞,尽管它们有几个独特的功能，在用作过继细胞疗法方面仍未开发，并且仅限于体外用于抗体生产。B细胞可以很容易地来源，它们具有出色的淋巴归巢能力，它们可以作为抗原呈递细胞（APC），提供树突状细胞（DC）的替代品，在临床上显示出有限的疗效。可溶性因子如IL-4和抗CD40抗体可增强其活性,生存,和B细胞的抗原呈递能力；然而，很难获得足够高浓度的这些生物制品以刺激体内B细胞。作为细胞参与剂的微贴片（MACE）是聚合物微粒，表面用抗CD40和抗IgM功能化，它可以附着于B细胞并同时接合多个B细胞受体（BCR）和CD40受体。通过MACE刺激这些受体，与游离抗体不同，增强了共刺激分子在B细胞表面的展示，B细胞活力增加，并在体外改善B细胞向T细胞的抗原呈递。通过MACE的B细胞活化进一步与可溶性IL-4和抗CD40协同。MACE还引起B细胞分泌T细胞趋化因子。静脉注射过继转移后，结合MACE的B细胞归巢于脾脏和淋巴结，抗原呈递给T细胞的关键位点。在小鼠皮下EG7-OVA肿瘤模型中，用卵清蛋白的CD4和CD8表位脉冲的MACE-B细胞的过继转移显着延迟了肿瘤进展，证明MACE赋予B细胞的功能益处。
