Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA; Cancer Center at Illinois (CCIL), Urbana, IL, 61801, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA; Carle College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA; Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Biomaterials. 2023 Feb;293:121972. doi: 10.1016/j.biomaterials.2022.121972. Epub 2022 Dec 16.
Adoptive T cell therapy has demonstrated great promise for treating cancer and other diseases. While extensive effort has been made to improve ex vivo expansion of T cells, strategies for maintaining the proliferation and function of T cells post adoptive transfer are still lacking. Here we report an injectable T cell-responsive macroporous hydrogel that enables in situ activation and expansion of T cells. The macroporous gel is composed of a polymeric network with dispersed macropores (∼150 μm) that are large enough to home T cells. In the presence of T cells that can gradually disrupt the gel network surrounding the macropores, activation cues can be gradually released for in situ activation and expansion of T cells. This T cell-responsive macroporous gel enables expansion of effector T cells in vivo, is stable over weeks upon subcutaneous injection, and results in enhanced CD8 T cell response and antitumor efficacy. We further show that the T cell-responsive macroporous gel could achieve comparable antitumor efficacy to conventional T cell therapy with a much lower cell dose. This injectable, T cell-responsive macroporous gel provides a platform for in vivo expansion of engineered T cells in a controlled manner, for timely and effective treatment of diseases.
过继性 T 细胞疗法在治疗癌症和其他疾病方面显示出巨大的潜力。虽然已经做出了大量努力来改善 T 细胞的体外扩增，但仍缺乏维持 T 细胞在过继转移后增殖和功能的策略。在这里，我们报告了一种可注射的 T 细胞响应性大孔水凝胶，可实现 T 细胞的原位激活和扩增。该大孔凝胶由具有分散大孔（约 150μm）的聚合物网络组成，大孔足够大可以容纳 T 细胞。在存在可以逐渐破坏大孔周围凝胶网络的 T 细胞的情况下，激活信号可以逐渐释放，以实现 T 细胞的原位激活和扩增。这种 T 细胞响应性大孔凝胶能够在体内扩增效应 T 细胞，在皮下注射数周后仍保持稳定，并增强 CD8 T 细胞反应和抗肿瘤功效。我们进一步表明，T 细胞响应性大孔凝胶可以实现与传统 T 细胞疗法相当的抗肿瘤功效，而所需细胞剂量要低得多。这种可注射的、T 细胞响应性的大孔水凝胶为工程化 T 细胞的体内扩增提供了一个可控的平台，可及时有效地治疗疾病。
